Non‐inherited maternal HLA alleles are associated with rheumatoid arthritis (2022)

Article Navigation

Volume 42 Issue 1

January 2003

Article Contents

  • Abstract

  • Methods

  • Results

  • Discussion

  • References

  • < Previous
  • Next >

Journal Article

S. Harney,

S. Harney

Search for other works by this author on:

Oxford Academic

J. Newton,

J. Newton

Search for other works by this author on:

Oxford Academic

A. Milicic,

A. Milicic

Search for other works by this author on:

Oxford Academic

M. A. Brown,

M. A. Brown

Search for other works by this author on:

Oxford Academic

B. P. Wordsworth

B. P. Wordsworth

Search for other works by this author on:

Oxford Academic

Google Scholar

(Video) Rheumatoid arthritis - causes, symptoms, diagnosis, treatment, pathology

Rheumatology, Volume 42, Issue 1, January 2003, Pages 171–174, https://doi.org/10.1093/rheumatology/keg059

Published:

01 January 2003

Article history

Received:

19 March 2002

Accepted:

28 June 2002

Published:

01 January 2003

  • PDF
  • Split View
  • Views
    • Article contents
    • Figures & tables
    • Video
    • Audio
    • Supplementary Data
  • Cite

    Cite

    S. Harney, J. Newton, A. Milicic, M. A. Brown, B. P. Wordsworth, Non‐inherited maternal HLA alleles are associated with rheumatoid arthritis, Rheumatology, Volume 42, Issue 1, January 2003, Pages 171–174, https://doi.org/10.1093/rheumatology/keg059

    Close

Search

Close

Search

Advanced Search

Search Menu

Abstract

Background. Rheumatoid arthritis (RA) is strongly associated with a series of HLA‐DRB1 alleles that encode a conserved sequence of amino acids (70Q/R K/R R A A74) in the DRβ1 chain, known as the shared epitope (SE). However 30% of patients are negative for DRB1*04 and 15% are SE‐negative. Exposure to these alleles as non‐inherited maternal antigens (NIMA) might explain this discrepancy. We undertook a family study to investigate the role of NIMA in RA.

Methods. One hundred families, including the RA proband and both parents, were recruited. HLA‐DRB1 genotyping was performed using an allele‐specific polymerase chain reaction by standard methods. The frequencies of NIMA and non‐inherited paternal antigens (NIPA) were compared using contingency tables and a two‐tailed P test. We then reviewed four previously published studies of NIMA in RA and conducted an analysis of the combined data

Results. We identified 36 families in which the proband was DRB1*04‐negative and 13 in which the proband lacked the SE. There was an excess of DRB1*04 and SE NIMA (P=0.05) compared with NIPA. Combined analysis with previous studies showed that 53/231 mothers (23%) versus 25/205 fathers (12%) had a non‐inherited DRB1*04 (P=0.003) and 30/99 mothers versus 18/101 fathers had a non‐inherited SE allele (P=0.03).

Conclusion. A role for HLA NIMA in RA is suggested by these results.

Rheumatoid arthritis, Shared epitope, Non‐inherited maternal alleles, HLA.

Rheumatoid arthritis (RA) is a polygenic disorder to which the HLA region contributes about 30% of the genetic component. It is associated with certain HLA‐DRB1 alleles encoding a conserved sequence of amino acids in the binding site of these antigen‐presenting molecules, often referred to as the shared epitope (SE) [1]. The strongest associations are with certain HLA‐DRB1*04 alleles (*0401, *0404, *0405 and *0408) but other SE‐positive DRB1 alleles (*0101, *0102 and *1001) are also associated with RA. However, because about 30% of patients are negative for DRB1*04 and 15% are SE negative, a unifying pathological mechanism has proven elusive. Recent observations suggest that biologically relevant exposure to HLA antigens may occur during fetal development and/or subsequently through the persistence (perhaps for life) of maternal cells in the offspring (‘microchimerism’). It has been suggested that persistent microchimerism may be involved in the pathogenesis of certain autoimmune diseases, such as scleroderma and thyroiditis [2, 3]. Autoimmune thyroid disease is particularly interesting because, like RA, it occurs more commonly in women and there is an increased incidence post‐partum. Thyroid disease is also more common in RA patients and their relatives than in the general population. We therefore feel that non‐inherited maternal HLA antigens (NIMA) may also play a role in RA. Previous reports have not uniformly confirmed this hypothesis, but few have had adequate statistical power to reject it [4–7]. We combined all previous reports, both positive and negative, to see if this effect was real. Although this was not ideal, we felt confident pooling these studies as they were remarkably similar from a number of viewpoints: all had probands with RA defined by the 1987 American College of Rheumatology criteria; all patients were European and thus belonged to a population in which the importance of the DRB1*04 is well established; and all the DRB1 typing was performed using the same method. Additionally, if you pool only the French and Dutch data (i.e. data for mainland Northern Europeans), the results are significant for the DRB1*04 data. Overall, in these studies the number of Southern Europeans included was very small, and this was important as DRB1*01 plays a bigger role than in British Caucasians

We therefore undertook a study of 100 nuclear families to investigate the possible involvement of NIMA in RA.

Methods

One hundred nuclear families (RA proband and both parents) were recruited from the Oxfordshire and Southwest UK regions. All the probands fulfilled the 1987 American College of Rheumatology criteria for RA [8]. The probands and both parents were genotyped for HLA‐DRB1 alleles, including DRB1*04 subtypes, by the polymerase chain reaction using sequence‐specific primers. Samples that were positive for DRB1*04 were then subtyped for an additional nine primers. The potential role of NIMA was investigated by comparing the frequencies of DRB1*04 NIMA and SE NIMA with those of the corresponding non‐inherited paternal antigens (NIPA). The results from four previous studies of the effects of NIMA in RA [4–7] were combined with those in our study for a combined analysis.

Statistical analysis

The frequencies of NIMA and NIPA were compared using contingency tables and a two‐tailed P test. We used Mietinnen's method for calculating confidence intervals. In the SE studies there were only 13 families but 26 pieces of data were used as both parents were included. Following our reviewer's comments, we did homogeneity tests (Table 1) and found that our data set was different from the Dutch and French data sets, so we re‐analysed their data separately.

Table 1.

Homogeneity tests

Study
Non‐inherited maternal and paternal allelesTransmitted vs non‐transmitted allelesPresent studyten Wolde [4]van der Horst [5]ECRAF familial [6]ECRAF sporadic [7]
NIMATrans912813850
NIMANot438315233158
NIPATrans4239523
NIPANot927365235159
Totals26797812681390
Expected values3.310.110.016.210.450.0
10.532.031.651.032.8158.0
1.54.74.67.44.823.0
10.632.231.851.433.0159.0
2679.078.0126.081.0390.0
χ29.60.30.40.60.5
4.11.10.00.00.0
4.01.50.60.30.0
0.20.80.60.00.1
17.93.81.51.00.7
Total24.9d.f.=12P=0.02
Study
Non‐inherited maternal and paternal allelesTransmitted vs non‐transmitted allelesPresent studyten Wolde [4]van der Horst [5]ECRAF familial [6]ECRAF sporadic [7]
NIMATrans912813850
NIMANot438315233158
NIPATrans4239523
NIPANot927365235159
Totals26797812681390
Expected values3.310.110.016.210.450.0
10.532.031.651.032.8158.0
1.54.74.67.44.823.0
10.632.231.851.433.0159.0
2679.078.0126.081.0390.0
χ29.60.30.40.60.5
4.11.10.00.00.0
4.01.50.60.30.0
0.20.80.60.00.1
17.93.81.51.00.7
Total24.9d.f.=12P=0.02

Open in new tab

Table 1.

Homogeneity tests

Study
Non‐inherited maternal and paternal allelesTransmitted vs non‐transmitted allelesPresent studyten Wolde [4]van der Horst [5]ECRAF familial [6]ECRAF sporadic [7]
NIMATrans912813850
NIMANot438315233158
NIPATrans4239523
NIPANot927365235159
Totals26797812681390
Expected values3.310.110.016.210.450.0
10.532.031.651.032.8158.0
1.54.74.67.44.823.0
10.632.231.851.433.0159.0
2679.078.0126.081.0390.0
χ29.60.30.40.60.5
4.11.10.00.00.0
4.01.50.60.30.0
0.20.80.60.00.1
17.93.81.51.00.7
Total24.9d.f.=12P=0.02
Study
Non‐inherited maternal and paternal allelesTransmitted vs non‐transmitted allelesPresent studyten Wolde [4]van der Horst [5]ECRAF familial [6]ECRAF sporadic [7]
NIMATrans912813850
NIMANot438315233158
NIPATrans4239523
NIPANot927365235159
Totals26797812681390
Expected values3.310.110.016.210.450.0
10.532.031.651.032.8158.0
1.54.74.67.44.823.0
10.632.231.851.433.0159.0
2679.078.0126.081.0390.0
χ29.60.30.40.60.5
4.11.10.00.00.0
4.01.50.60.30.0
0.20.80.60.00.1
17.93.81.51.00.7
Total24.9d.f.=12P=0.02

Open in new tab

Results

We identified 36 families in which the proband was HLA‐DRB1*04‐negative and only 13 in which the proband was SE‐negative. There was a non‐significant excess of DRB1*04 NIMA compared with NIPA (Table 2) and a significant excess of SE‐positive NIMA vs NIPA (P=0.05). The results of the combined analysis are shown in Table 2. There was a significant excess of DRB1*04 NIMA (23%) vs NIPA (12%), with an odds ratio of 2.1 (95% confidence interval 1.3–3.6) The incomplete data from some previous studies allowed us to undertake only a limited analysis of SE NIMA. Overall, 112 SE‐negative probands were identified; a significant excess of mothers (30%) compared with fathers (18%) carried an SE‐positive NIMA (P=0.04). As the French and Dutch data were remarkably similar and homogeneous when tests were done, we also combined these and found a similar significant result, with a P value of 0.01 (Table 3).

Table 2.

Comparison of NIMA and NIPA in DRB1*04‐ and SE‐negative patients with RA

(Video) Immunology of the rheumatoid joint
StudyNo. of DRB1*04‐ negative patientsDRB1*04‐ positive NIMADRB1*04‐ negative NIPAOdds ratio (95% CI)
Present study (UK)3612/366/362.5 (0.8–7.5)
ten Wolde et al., The Netherlands [4]5012/502/294.3 (0.9–20.6)
van der Horst et al., The Netherlands [5]398/393/393.1 (0.8–12.7)
Barrera et al., ECRAF (sporadic) [6]7213/659/611.44 (0.5–3.7)
Barrera et al., ECRAF (multicase) [7]518/415/401.94 (0.6–6.5)
Above five studies combined24853/23125/2052.1 (1.3–3.6)*
No. of SE patientsSE+ NIMASE+ NIPAOdds ratio (95% CI)
Present study (UK)139/134/135.1 (1.0–25.6)
van der Horst et al., The Netherlands [5]254/252/252.2 (0.4–13.2)
Barrera et al., ECRAF (sporadic) [6]4310/386/371.9 (0.6–5.7)
Barrera et al., ECRAF (multicase) [7]317/236/261.5 (0.4–5.2)
Above four studies combined11230/9918/1012.0 (1.04–3.9)**
StudyNo. of DRB1*04‐ negative patientsDRB1*04‐ positive NIMADRB1*04‐ negative NIPAOdds ratio (95% CI)
Present study (UK)3612/366/362.5 (0.8–7.5)
ten Wolde et al., The Netherlands [4]5012/502/294.3 (0.9–20.6)
van der Horst et al., The Netherlands [5]398/393/393.1 (0.8–12.7)
Barrera et al., ECRAF (sporadic) [6]7213/659/611.44 (0.5–3.7)
Barrera et al., ECRAF (multicase) [7]518/415/401.94 (0.6–6.5)
Above five studies combined24853/23125/2052.1 (1.3–3.6)*
No. of SE patientsSE+ NIMASE+ NIPAOdds ratio (95% CI)
Present study (UK)139/134/135.1 (1.0–25.6)
van der Horst et al., The Netherlands [5]254/252/252.2 (0.4–13.2)
Barrera et al., ECRAF (sporadic) [6]4310/386/371.9 (0.6–5.7)
Barrera et al., ECRAF (multicase) [7]317/236/261.5 (0.4–5.2)
Above four studies combined11230/9918/1012.0 (1.04–3.9)**

Open in new tab

Table 2.

Comparison of NIMA and NIPA in DRB1*04‐ and SE‐negative patients with RA

StudyNo. of DRB1*04‐ negative patientsDRB1*04‐ positive NIMADRB1*04‐ negative NIPAOdds ratio (95% CI)
Present study (UK)3612/366/362.5 (0.8–7.5)
ten Wolde et al., The Netherlands [4]5012/502/294.3 (0.9–20.6)
van der Horst et al., The Netherlands [5]398/393/393.1 (0.8–12.7)
Barrera et al., ECRAF (sporadic) [6]7213/659/611.44 (0.5–3.7)
Barrera et al., ECRAF (multicase) [7]518/415/401.94 (0.6–6.5)
Above five studies combined24853/23125/2052.1 (1.3–3.6)*
No. of SE patientsSE+ NIMASE+ NIPAOdds ratio (95% CI)
Present study (UK)139/134/135.1 (1.0–25.6)
van der Horst et al., The Netherlands [5]254/252/252.2 (0.4–13.2)
Barrera et al., ECRAF (sporadic) [6]4310/386/371.9 (0.6–5.7)
Barrera et al., ECRAF (multicase) [7]317/236/261.5 (0.4–5.2)
Above four studies combined11230/9918/1012.0 (1.04–3.9)**
StudyNo. of DRB1*04‐ negative patientsDRB1*04‐ positive NIMADRB1*04‐ negative NIPAOdds ratio (95% CI)
Present study (UK)3612/366/362.5 (0.8–7.5)
ten Wolde et al., The Netherlands [4]5012/502/294.3 (0.9–20.6)
van der Horst et al., The Netherlands [5]398/393/393.1 (0.8–12.7)
Barrera et al., ECRAF (sporadic) [6]7213/659/611.44 (0.5–3.7)
Barrera et al., ECRAF (multicase) [7]518/415/401.94 (0.6–6.5)
Above five studies combined24853/23125/2052.1 (1.3–3.6)*
No. of SE patientsSE+ NIMASE+ NIPAOdds ratio (95% CI)
Present study (UK)139/134/135.1 (1.0–25.6)
van der Horst et al., The Netherlands [5]254/252/252.2 (0.4–13.2)
Barrera et al., ECRAF (sporadic) [6]4310/386/371.9 (0.6–5.7)
Barrera et al., ECRAF (multicase) [7]317/236/261.5 (0.4–5.2)
Above four studies combined11230/9918/1012.0 (1.04–3.9)**

Open in new tab

Table 3.

Data from Dutch and French data sets

Studies (all referred to in [3])No. of DRB1*04‐ negative patientsDRB1*04‐ positive NIMADRB1*04‐ negative NIPAOdds ratio (95% CI)
ten Wolde et al., The Netherlands [4]5012/502/294.3 (0.9–20.6)
van der Horst et al., The Netherlands [5]398/393/393.1 (0.8–12.7)
Barrera et al., ECRAF (sporadic) [6]7213/659/611.44 (0.5–3.7)
Barrera et al., ECRAF (multicase) [7]518/415/401.94 (0.6–6.5)
Above four studies combined21241/19519/1692.1 (1.2–3.8) (P=0.01)
Studies (all referred to in [3])No. of DRB1*04‐ negative patientsDRB1*04‐ positive NIMADRB1*04‐ negative NIPAOdds ratio (95% CI)
ten Wolde et al., The Netherlands [4]5012/502/294.3 (0.9–20.6)
van der Horst et al., The Netherlands [5]398/393/393.1 (0.8–12.7)
Barrera et al., ECRAF (sporadic) [6]7213/659/611.44 (0.5–3.7)
Barrera et al., ECRAF (multicase) [7]518/415/401.94 (0.6–6.5)
Above four studies combined21241/19519/1692.1 (1.2–3.8) (P=0.01)

Open in new tab

Table 3.

Data from Dutch and French data sets

Studies (all referred to in [3])No. of DRB1*04‐ negative patientsDRB1*04‐ positive NIMADRB1*04‐ negative NIPAOdds ratio (95% CI)
ten Wolde et al., The Netherlands [4]5012/502/294.3 (0.9–20.6)
van der Horst et al., The Netherlands [5]398/393/393.1 (0.8–12.7)
Barrera et al., ECRAF (sporadic) [6]7213/659/611.44 (0.5–3.7)
Barrera et al., ECRAF (multicase) [7]518/415/401.94 (0.6–6.5)
Above four studies combined21241/19519/1692.1 (1.2–3.8) (P=0.01)
Studies (all referred to in [3])No. of DRB1*04‐ negative patientsDRB1*04‐ positive NIMADRB1*04‐ negative NIPAOdds ratio (95% CI)
ten Wolde et al., The Netherlands [4]5012/502/294.3 (0.9–20.6)
van der Horst et al., The Netherlands [5]398/393/393.1 (0.8–12.7)
Barrera et al., ECRAF (sporadic) [6]7213/659/611.44 (0.5–3.7)
Barrera et al., ECRAF (multicase) [7]518/415/401.94 (0.6–6.5)
Above four studies combined21241/19519/1692.1 (1.2–3.8) (P=0.01)

Open in new tab

Discussion

HLA molecules are crucial in the definition of self and are key determinants of transplant success. Their role in susceptibility to RA is well established but the disease processes involved have not yet been clarified. Our results, combined with previous studies, strongly suggest that HLA NIMA may also be involved in RA.

It has already been shown that NIMA can influence immunologically mediated processes. Thus, Burlingham et al. [9] showed that graft survival for siblings mismatched with the donor for the NIMA haplotype was similar to that of graft survival in HLA‐identical donors. It has been suggested that exposure to the NIMA haplotype in utero by transplacental transfusion may lead to tolerance. Maternal cells may persist in the fetus (and vice versa) in a process known as microchimerism, but whether this is necessary for tolerance to develop is unclear. Srivatsa et al. [10] recently demonstrated striking microchimerism in autoimmune thyroid disease, suggesting that it may play a significant role in autoimmunity. Microchimerism in thyroid disease is particularly interesting because of the high post‐partum incidence of subclinical thyroiditis. Thyroid disease and RA have several parallels: both are more common in women and tend to flare or present post‐partum. Nelson et al. [2] have highlighted the role of microchimerism in scleroderma. In contrast, Nelson [3] recently questioned whether microchimerism was just a remnant of healthy pregnancy. On the other hand, another article has reported a patient with a terminal thymic tumour that regressed after she received a stem‐cell infusion of her daughter's cells, which were mismatched for NIMA. However, the mechanisms by which NIMA might influence susceptibility to RA are as unclear as the role HLA molecules play in the process. The mechanisms by which B cell unresponsiveness to NIMA is induced are not yet established [11]. Microchimerism is found frequently in the blood of healthy parous women, and healthy offspring often possess maternal cells. Although we have been able to demonstrate a significant excess of DRB1*04 and SE NIMA in RA families, this effect is relatively weak. We have shown that, with increased study numbers, this effect exists. However, to date there has been no large study in RA to prove this hypothesis definitively. As highlighted recently by Nelson, the role of NIMA in human health and disease is worth further investigation [2] and appears to play a significant role in the pathogenesis of RA.

This work was supported by the Arthritis Research Campaign and the Grenville Bequest.

References

1

Gregersen PK, Silver J, Winchester RJ. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis.

Arthritis Rheum

1987

;

30

:

1205

–13.

2

Nelson JL, Furst DE, Maloney S et al. Microchimerism and HLA‐compatible relationships of pregnancy in scleroderma.

Lancet

1998

;

351

:

559

–62.

3

Nelson J. Microchimerism: expanding new horizons in human health or incidental remnant of pregnancy?

Lancet

2001

;

358

:

2011

–2.

4

ten Wolde S, Breedveld FC, de Vries RR et al. Influence of non‐inherited maternal HLA antigens on occurrence of rheumatoid arthritis.

Lancet

1993

;

341

(Video) Rheumatoid Arthritis (RA) Signs & Symptoms (& Associated Complications)

:

200

–2.

5

van der Horst‐Bruinsma IE, Hazes JM, Schreuder GM et al. Influence of non‐inherited maternal HLA‐DR antigens on susceptibility to rheumatoid arthritis.

Ann Rheum Dis

1998

;

57

:

672

–5.

6

Barrera P, Balsa A, Alves H et al. Noninherited maternal antigens do not play a role in rheumatoid arthritis susceptibility in Europe. European Consortium on Rheumatoid Arthritis Families.

Arthritis Rheum

2000

;

43

:

758

–64.

7

Barrera P, Balsa A, Alves H et al. Noninherited maternal antigens do not increase the susceptibility for familial rheumatoid arthritis. European Consortium on Rheumatoid Arthritis Families (ECRAF).

J Rheumatol

2001

;

28

:

968

–74.

8

Arnett F, Edworthy SM, Bloch DA. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.

Arthritis Rheum

1988

;

31

:

315

–24.

9

Burlingham WJ, Grailer AP, Heisey DM et al. The effect of tolerance to noninherited maternal HLA antigens on the survival of renal transplants from sibling donors.

N Engl J Med

1998

;

339

:

1657

–64.

10

Srivatsa B, Srivatsa S, Johnson KL, Samura O, Lee SL, Bianchi DW. Microchimerism of presumed fetal origin in thyroid specimens from women: a case–control study.

Lancet

2001

;

358

:

2034

–8.

11

Claas FH, Gijbels Y, van der Velden‐de Munck J, van Rood JJ. Induction of B cell unresponsiveness to noninherited maternal HLA antigens during fetal life.

Science

1988

;

241

:

1815

–7.

(Video) Rheumatoid Arthritis Update: 2020

© British Society for Rheumatology

© British Society for Rheumatology

Issue Section:

Original Papers

Download all slides

Advertisement

Citations

Views

442

Altmetric

×

Email alerts

Article activity alert

Advance article alerts

New issue alert

Subject alert

Receive exclusive offers and updates from Oxford Academic

Related articles in

Citing articles via

Google Scholar

Crossref

  • Latest

  • Most Read

  • Most Cited

IRF6 mutation in systemic sclerosis—innocent bystander or contributing factor?
Point-of-care ultrasonography in large vessel involvement by IgG4-related disease: an opportunity for monitoring?
“What is fuelling the immune response in systemic lupus erythematosus?” Evaluating the key metabolites driving plasmablast differentiation
Macrophages as determinants and regulators of fibrosis in systemic sclerosis
Lupus myocarditis: review of current diagnostic modalities and their application in clinical practice

FAQs

Which HLA type is associated with rheumatoid arthritis? ›

HLA alleles and susceptibility to rheumatoid arthritis — Both linkage and association studies have established that the human leukocyte antigen (HLA) DRB1 gene is the major genetic susceptibility locus for rheumatoid arthritis (RA).

Is rheumatoid arthritis an inherited disease? ›

"RA, like many autoimmune diseases, is quite heritable and unfortunately tends to cluster in families," says Hu. "Many genetic studies have gone into identifying genes that predispose individuals to the risk of RA."

What type of inheritance is rheumatoid arthritis? ›

While RA isn't hereditary, genetics can increase your chances of developing this autoimmune disorder. Researchers have established several genetic markers that can increase this risk. These genes are associated with the immune system, chronic inflammation, and with RA in particular.

Is arthritis hereditary or genetic? ›

The most common type: Osteoarthritis

Around 40 to 65% of osteoarthritis has a genetic component, with a stronger link for hand and hip cases. Dr. Syed assures that there is not a singular gene that causes cases of osteoarthritis. “Multiple genes are involved,” he comments.

How does HLA cause rheumatoid arthritis? ›

The molecular basis for the HLA-DRB1 association with RA is still unclear. One prevailing hypothesis is that the RA-associated HLA-DR molecules present self-antigens to autoaggressive T cells, which subsequently induce an inflammatory response that leads to the development of arthritis.

Is HLA-B27 positive in rheumatoid arthritis? ›

HLA-B27 is not associated with RA.

How do you confirm rheumatoid arthritis? ›

There is no one blood test or physical finding to confirm the diagnosis. During the physical exam, your doctor will check your joints for swelling, redness and warmth. He or she may also check your reflexes and muscle strength.

What is the main cause of rheumatoid arthritis? ›

Rheumatoid arthritis is an autoimmune condition, which means it's caused by the immune system attacking healthy body tissue. However, it's not yet known what triggers this. Your immune system normally makes antibodies that attack bacteria and viruses, helping to fight infection.

Can you test for rheumatoid arthritis gene? ›

Autoantibodies and genes

Blood tests commonly performed on people with suspected RA include tests to check whether the person carries antibodies (proteins made by the body's immune system) associated with RA, called “rheumatoid factor” and “anti-cyclic citrullinated peptide” (anti-CCP).

What are the 3 types of rheumatoid arthritis? ›

Types of Rheumatoid Arthritis – Seropositive or Seronegative RA
  • Rheumatoid Factor Positive (Seropositive) RA. ...
  • Rheumatoid Factor Negative (Seronegative) RA. ...
  • Overlapping Conditions.
11 Feb 2016

Why is rheumatoid arthritis more common in females? ›

Abstract. Rheumatoid arthritis (RA) is two- to three-fold more frequent in women than in men and a strong association with sex hormones has been demonstrated. There is strong evidence that autoimmunity is under genetic control, and genes in sexual chromosomes can play a role in supporting the female prevalence.

Is rheumatoid arthritis dominant or recessive? ›

Our investigation suggests that familial RA is the effect, in part, of an inherited autosomal dominant susceptibility gene with incomplete penetrance rather than that of a recessive gene.

How can you prevent hereditary arthritis? ›

How to reduce your risk of arthritis
  1. Stay at a healthy weight. Extra pounds put pressure on weight-bearing joints like hips and knees. ...
  2. Control your blood sugar. ...
  3. Exercise. ...
  4. Stretch. ...
  5. Avoid injury. ...
  6. Quit smoking. ...
  7. Eat fish twice a week. ...
  8. Get routine preventive care.

How can you prevent rheumatoid arthritis? ›

There's no way to prevent RA, but you can lower your chances if you: Quit smoking. It's the one sure thing besides your genes that boosts your odds of getting RA. Some studies show it also can make the disease get worse faster and lead to more joint damage, especially if you're ages 55 or younger.

How quickly does rheumatoid arthritis spread? ›

The symptoms of rheumatoid arthritis often develop gradually over several weeks, but some cases can progress quickly over a number of days. The symptoms vary from person to person. They may come and go, or change over time. You may experience flares when your condition deteriorates and your symptoms become worse.

What does HLA mean? ›

HLA stands for human leukocyte antigens. HLA are proteins—or markers—on most cells in your body. Your immune system uses HLA to see which cells belong in your body and which do not.

How many HLA types are there? ›

HLA are proteins that are located on the surface of the white blood cells and other tissues in the body. There are three general groups of HLA, they are HLA-A,HLA-B and HLA-DR.

What do you mean by HLA typing? ›

Human leukocyte antigen (HLA) typing is used to match patients and donors for bone marrow or cord blood transplants. HLA are proteins -- or markers -- found on most cells in your body. Your immune system uses these markers to recognize which cells belong in your body and which do not.

What does it mean to test positive for HLA? ›

A positive test means HLA-B27 is present. It suggests a greater-than-average risk for developing or having certain autoimmune disorders. An autoimmune disorder is a condition that occurs when the immune system mistakenly attacks and destroys healthy body tissue.

What causes HLA-B27 positive? ›

The presence of HLA-B27 is associated with certain autoimmune and immune-mediated diseases, including: ankylosing spondylitis, which causes inflammation of the bones in your spine. reactive arthritis, which causes inflammation of your joints, urethra, and eyes, and sometimes lesions on your skin.

What does it mean if you are HLA-B27 negative? ›

If an HLA-B27 test is negative, then the marker was not detected. This does not mean, however, that the person tested does not have the suspected condition since people who do not have the HLA-B27 antigen can also develop these autoimmune diseases.

What are usually the first signs of rheumatoid arthritis? ›

Signs and symptoms of rheumatoid arthritis may include: Tender, warm, swollen joints. Joint stiffness that is usually worse in the mornings and after inactivity. Fatigue, fever and loss of appetite.

How do you permanently treat rheumatoid arthritis? ›

Although there's no cure for rheumatoid arthritis, early treatment and support (including medicine, lifestyle changes, supportive treatments and surgery) can reduce the risk of joint damage and limit the impact of the condition. Your treatment will usually involve care from your GP and several different specialists.

Does rheumatoid arthritis show up on xray? ›

For decades, X-rays were used to help detect rheumatoid arthritis (RA) and monitor for worsening bone damage. In the early stages of RA, however, X-rays may appear normal although the disease is active, making the films useful as a baseline but not much help in getting a timely diagnosis and treatment.

Who is at risk for developing rheumatoid arthritis? ›

People born with specific genes are more likely to develop RA. These genes, called HLA (human leukocyte antigen) class II genotypes, can also make your arthritis worse. The risk of RA may be highest when people with these genes are exposed to environmental factors like smoking or when a person is obese. Smoking.

What is positive rheumatoid factor? ›

A positive rheumatoid factor test result indicates that a high level of rheumatoid factor was detected in your blood. A higher level of rheumatoid factor in your blood is closely associated with autoimmune disease, particularly rheumatoid arthritis.

What is Stage 1 rheumatoid arthritis? ›

The stage 1 is the early stage of rheumatoid arthritis. At this stage, patients experience joint tissue inflammation that causes joint pain, stiffness, swelling, redness, and tenderness. The joint lining known as the synovium becomes inflamed. There's no damage to the bones.

Is rheumatoid arthritis life threatening? ›

Can people die from rheumatoid arthritis? A person cannot die from rheumatoid arthritis (RA). However, RA can increase the risk of developing complications that may compromise a person's overall health. RA is a chronic medical condition that involves increased levels of inflammation in tissues throughout the body.

What parts of the body does rheumatoid arthritis affect? ›

The joints most often affected by RA are in the hands, wrists, feet, ankles, knees, shoulders, and elbows. Symptoms may include joint pain, stiffness, and swelling; decreased and painful movement; bumps over small joints; and fatigue or fever.

Can arthritis be reversed? ›

A person cannot reverse arthritis, but they can manage their symptoms. Arthritis commonly causes joint inflammation with swelling, pain, stiffness, and decreased range of motion. According to the Arthritis Foundation, almost 60 million adults and 300,000 children have some form of arthritis.

Can rheumatoid arthritis affect your legs? ›

Cysts, which may develop behind affected knees, can rupture, causing pain and swelling in the lower legs. Up to 30% of people with rheumatoid arthritis have hard bumps just under the skin (called rheumatoid nodules), usually near sites of pressure (such as the back of the forearm near the elbow).

What's the difference between arthritis and rheumatoid arthritis? ›

rheumatoid arthritis. Osteoarthritis, the most common form of arthritis, involves the wearing away of the cartilage that caps the bones in your joints. Rheumatoid arthritis is a disease in which the immune system attacks the joints, beginning with the lining of joints.

What are the 4 stages of rheumatoid arthritis? ›

The four stages of rheumatoid arthritis are known as synovitis, pannus, fibrous ankylosis, and bony ankylosis.
  • Stage I: Synovitis. During stage I, you may start having mild symptoms, including joint pain and joint stiffness. ...
  • Stage II: Pannus. ...
  • Stage III: Fibrous Ankylosis. ...
  • Stage IV: Bony Ankylosis.
12 Oct 2021

Can you lose weight with rheumatoid arthritis? ›

The same pro-inflammatory cytokines, such as TNF, that damage the joint tissue in people with RA can also lead to weight loss, muscle wasting and weakness.

Can estrogen help with rheumatoid arthritis? ›

The administration of estrogens may have a protective effect on RA development or in the onset of disease, delaying it. Also, experimental evidence suggests that estrogens demonstrated anti-inflammatory activity in animal models of RA.

Which arthritis is common in female? ›

Osteoarthritis (OA) is the most common form of arthritis among older people generally, but osteoarthritis tends to affect women more than men for a variety of reasons including anatomy and genetics. Women's joints are more elastic and allow for freer joint motion.

Is seronegative rheumatoid arthritis hereditary? ›

Risk factors

Some people appear to be more likely to develop a form of RA. The risk factors are similar for seropositive and seronegative RA, and they include: genetic factors and family history.

Is rheumatoid arthritis an autoimmune disease? ›

Rheumatoid arthritis is an autoimmune disease. This means your immune system (which usually fights infection) attacks the cells that line your joints by mistake, making the joints swollen, stiff and painful. Over time, this can damage the joints, cartilage and nearby bone.

Which of the following immune response is responsible for rheumatoid arthritis? ›

So, the correct answer is 'Cell-mediated immune response'

What does HLA-DR4 do? ›

When the genetic marker HLA-DR4, a human leukocyte antigen that is a genetic anomaly, is found in white blood cells there is a risk for developing RA. The marker's function is to distinguish one's own cells from foreign invaders. If HLA-DR4 cannot differentiate between the two, it may attack self cells.

What is associated with HLA-B27? ›

HLA-B27 is associated with the pustular form of psoriasis and weakly associated with peripheral psoriatic arthritis. In the presence of spondylitis-associated with psoriasis, 60-70% of these cases are HLA-B27 positive.

What is HLA drw4? ›

HLA-DR4 (DR4) is an HLA-DR serotype that recognizes the DRB1*04 gene products. The DR4 serogroup is large and has a number of moderate frequency alleles spread over large regions of the world.

Which autoimmune disease is associated with the gene HLA DR2? ›

DR2 serotypes are associated with Goodpasture syndrome, systemic lupus erythematosus, multiple sclerosis, and narcolepsy, tuberculoid leprosy (multi-drug-resistant tuberculosis or leprosy), ulcerative colitis(Japanese), primary biliary cirrhosis and autoimmune hepatitis.

How common is HLA-DR4? ›

A study by Russell et al. [123], reported a frequency of HLA-DR4 antigen of 70% among 20 patients with hydralazine-related lupus compared with a frequency of 33% in the general population. Six of these 20 patients had been included in the 1980 study by Batchelor et al.

Is HLA-DR4 a gene? ›

It is estimated that about one third of genetic risks of RA are located on major histocompatibility complex (MHC) and allelic variation in HLA-DR4, which is a serotype of Human Leukocyte Antigen (HLA)-DR gene, it encode chain molecule number 13 of MHC class II.

How do you test for HLA gene? ›

To find out if you are a carrier with the HLA – DR gene there's a blood test one can get called HLA DR typing. The word “antigen” shows up both in Human Leukocyte ANTIGEN and in the definition of toxin. In very simple terms, an antigen is a molecule which can produce an immunologic response in the body.

What diseases are associated with HLA-B27 positive? ›

OTHER DISEASE ASSOCIATIONS

84% of HLA-B27 positive patients with AAU have other B27-associated diseases—specifically Reiter's syndrome, ankylosing spondylitis or psoriatic arthritis. Conversely, about 20–30% of patients with ankylosing spondylitis or Reiter's syndrome develop AAU.

What causes HLA-B27 positive? ›

The presence of HLA-B27 is associated with certain autoimmune and immune-mediated diseases, including: ankylosing spondylitis, which causes inflammation of the bones in your spine. reactive arthritis, which causes inflammation of your joints, urethra, and eyes, and sometimes lesions on your skin.

What does it mean if you are HLA-B27 negative? ›

If an HLA-B27 test is negative, then the marker was not detected. This does not mean, however, that the person tested does not have the suspected condition since people who do not have the HLA-B27 antigen can also develop these autoimmune diseases.

How many HLA genes are there? ›

The HLA region lies on the short arm of chromosome six at position 6p21. 3. The classical MHC spans 3.6 megabases (Mb) and comprises more than 200 genes, including many immune system genes, but also many genes without any known immune function.

What is positive rheumatoid factor? ›

A positive rheumatoid factor test result indicates that a high level of rheumatoid factor was detected in your blood. A higher level of rheumatoid factor in your blood is closely associated with autoimmune disease, particularly rheumatoid arthritis.

Does everyone have HLA-DRB1? ›

DRB1 is present in all individuals. Allelic variants of DRB1 are linked with either none or one of the genes DRB3, DRB4 and DRB5. There are 5 related pseudogenes: DRB2, DRB6, DRB7, DRB8 and DRB9. Prevalence of the HLA-DRB1*10:01 allele was greatly increased in people with anti-IgLON5 disease.

Does HLA cause autoimmune disease? ›

Human leukocyte antigen (HLA) is the main genetic factor related to autoimmune diseases, accounting for a half of known genetic predisposition [6].

Is HLA hereditary? ›

The HLA system is inherited in a Mendelian manner and extensively polymorphic; its recombination rate is low; mutation has not been observed in family studies; and antigen frequencies are known for many different ethnic groups.

What does HLA positive mean? ›

A positive test means HLA-B27 is present. It suggests a greater-than-average risk for developing or having certain autoimmune disorders. An autoimmune disorder is a condition that occurs when the immune system mistakenly attacks and destroys healthy body tissue.

Videos

1. Is Rheumatoid Arthritis genetic?
(BJC Health)
2. Rheumatoid Arthritis, how it happens
(UWDeptMedicine)
3. RNL 2022: Rheumatoid Arthritis - Best Management
(RheumNow)
4. Rheumatoid Arthritis (Part 3): Pathophysiology
(Medicosis Perfectionalis)
5. The biological diversity of self: Microchimerism | Lee Nelson
(Evolutionary Medicine)
6. Is Arthritis Genetic
(Fitness For Woman)

Top Articles

Latest Posts

Article information

Author: Catherine Tremblay

Last Updated: 11/14/2022

Views: 6394

Rating: 4.7 / 5 (47 voted)

Reviews: 94% of readers found this page helpful

Author information

Name: Catherine Tremblay

Birthday: 1999-09-23

Address: Suite 461 73643 Sherril Loaf, Dickinsonland, AZ 47941-2379

Phone: +2678139151039

Job: International Administration Supervisor

Hobby: Dowsing, Snowboarding, Rowing, Beekeeping, Calligraphy, Shooting, Air sports

Introduction: My name is Catherine Tremblay, I am a precious, perfect, tasty, enthusiastic, inexpensive, vast, kind person who loves writing and wants to share my knowledge and understanding with you.