Rheumatoid Factor Positive Rheumatoid Arthritis Research Articles

Prevalence and severity of periodontitis in patients with established rheumatoid arthritis and osteoarthritis.

Introduction:Periodontitis is associated with many chronic health conditions including diabetes, cardiovascular disease, and rheumatoid arthritis (RA). RA and periodontitis have similarities in inflammatory mechanism, morphology, and histopathology. Osteoarthritis (OA) is a chronic, multifactorial degenerative disease characterized by the deterioration of cartilage in joints.Objective:The aim of this study was to evaluate the prevalence and severity of periodontal disease in patients with established RA and OA.Materials and Methods:A total of 200 patients reporting to the Department of Orthopaedics, KIMSDU, Karad were included in the study. Patients were divided into two groups: Group 1 that included 100 patients with established RA diagnosed according to American College of Rheumatology (ACR) classification 1987 criteria and Group 2 that comprised 100 patients diagnosed with OA. Demographic profile, medical and dental history, oral hygiene practices, and smoking status of study participants were recorded. Periodontal status of the patients were evaluated using the simplified oral hygiene index (OHI-S), Loe and Silness gingival index (GI), probing pocket depth (PPD), and clinical attachment level (CAL). On the basis of the CAL score periodontitis severity was defined as slight, moderate, and severe. Rheumatoid Factor (RF) and C-reactive protein (CRP) were considered as a serological marker in RA. Serological tests were performed to measure RF and CRP. Periodontal parameters and serological tests were correlated.Results:This study reported 45% severe periodontitis prevalence in RA compared to OA group, which was 33%. Severity of periodontitis is significantly greater in RF positive RA group with mean CAL 5.38 mm compared to RF negative RA group with mean CAL 2.81 mm (P = 0.001). There was moderate positive correlation found between RF titer and severity of periodontitis (r = 0.311).Conclusion:The severity of periodontitis was significantly higher among the patients with established RA as compared to patients with OA. RF positive patients had higher periodontal disease compared to RF negative patients. There was an increase in the mean clinical attachment loss with increase in RF titer.

Association between polymorphisms of interleukin 12 and rheumatoid arthritis associated biomarkers in a Chinese population

IntroductionThe aim of the present study was to examine the association between polymorphisms of interleukin 12 (IL-12) and rheumatoid arthritis (RA) associated biomarkers in a Chinese population. Materials and methodsWe studied IL-12A rs2243115 T/G and IL-12B rs3212227 A/C polymorphisms in 615 RA patients and 839 controls in a Chinese population. Genotyping was done by a custom-by-design 48-Plex SNPscan™ Kit. The plasma level of IL-12 was measured by an enzyme-linked immune-sorbent assay in 90 RA patients and 90 controls. Clinical data with other potential diagnostic value were provided by the physicians. ResultsA significantly increased risk for RA associated with the IL-12A rs2243115 GG (GG versus TT: OR=4.81, 95% CI 1.33–17.36, P=0.017; and GG versus TG+TT: OR=4.55, 95% CI 1.27–16.36, P=0.020) genotype was evident among rheumatoid factor (RF) negative patients, and with the IL-12B rs3212227 AC (AC versus AA) and AC+CC (AC+CC versus AA) genotypes were evident among older patients (OR=1.48, 95% CI 1.06–2.06, P=0.020), RF positive patients (OR=1.35, 95% CI 1.04–1.75, P=0.026) and anti-cyclic citrullinated peptide antibodies (ACPA) negative patients (OR=1.53, 95% CI 1.11–2.10, P=0.009). The plasma level of IL-12 was significantly higher in RA patients (P<0.001). IL-12 plasma level of IL-12A rs2243115 TT (P<0.001) and IL-12B rs3212227 C allele (P<0.001) were significantly higher in RA patients than controls respectively. The plasma level of IL-12 of RF positive RA patients was significantly higher than RF negative patients (P=0.008), especially in rs3212227 AC patients (P=0.01). ConclusionsThese findings suggested that the functional single nucleotide polymorphism (SNP) IL-12A rs2243115 GG genotype may increase the risk of RA in RF negative patients, and the IL-12B rs3212227 AC and AC+CC genotypes are associated with RA risk in older patients, RF positive patients and ACPA negative patients. The IL-12A rs2243115 T/G and IL-12B rs3212227 A/C allele might also impact the inflammatory reaction of IL-12 in patients with RA.

Changes and sex differences in patient reported outcomes in rheumatoid factor positive RA–results from a community based study

BackgroundPatient reported outcomes (PROs) are important measures in rheumatoid arthritis (RA). A register of patients with RA from all rheumatology care providers in Malmö, Sweden, was established in 1997 and has been continually updated. This register includes virtually all the RA patients in the area. The aim of this study was to analyse PROs in surveys of this population conducted between 1997 and 2009, and to assess differences in treatment and outcome in male and female patients.MethodIn 1997, 2002, 2005 and 2009, questionnaires were sent to the RA patients in the register (n = 1016 in 1997; n = 916 in 2002; n = 1625 in 2005; n = 1700 in 2009). Response rates varied between 62 % and 74 %, and 72-74 % was women. Questionnaire data included medication and measures of disability and health related quality of life. Data on rheumatoid factor (RF) tests were retrieved from the databases of the two clinical immunology laboratories in the area. In order to limit the impact of changes in the case mix over time, the study was restricted to RF positive patients. The analyses were stratified by sex.ResultsPatients reported less severe outcomes for all measures in the later surveys compared to 1997, and patients’ global disease activity assessment and self-reported pain were further improved in 2009 compared to 2005. Treatment with biologics increased over time from 1997 (none) to 2009 (29%), with no difference between men and women. Visual analogue scales (0-100) for patients’ global assessment of disease activity [mean 45 (95 % CI (45-47) vs. 38 (35-40)] and pain [mean 46 (44-49) vs. 38 (36-40)] decreased from 1997 to 2009, with numerically greater improvement in male patients. The mean SF-36 physical component scores also improved, and were higher in men than in women in all surveys.ConclusionPharmacologic treatment of RA became more extensive over time, and there was improvement in all PROs. Despite similar treatment, male patients reported better outcomes, in particular for pain and physical function, compared to female patients. We suggest that patient reported outcomes should be reported separately in male and female patients with RA.

Cardiovascular risk induced by low-dose corticosteroids in rheumatoid arthritis: A systematic literature review

Objectives To assess the association between cardiovascular (CV) risk and low-dose corticosteroids (LD-CT, defined as a daily dose < 10 mg/day of prednisone) in rheumatoid arthritis (RA) patients. Methods Data source: A systematic review of the literature up to June 2009 was performed. Data extraction: (1) cardiovascular risk factors: high blood pressure, glycemia and lipid profile, carotid intima-media thickness, pulse-wave velocity, ventricular function; (2) “hard” outcomes: heart failure (HF), stroke, myocardial infarction (MI) or mortality. Data analysis: descriptive, comparing CV risk between LD-CT-treated RA patients and LD-CT-non-treated RA patients. Results Of the 1138 screened reports, the literature search identified 37 assessing CV risk in LD-CT treated RA. The analysis showed a protective effect on serum lipid profile, an increase of insulin resistance or glycemia, probably no effect on blood pressure, no effect on atherosclerosis, discrepancies regarding arterial stiffness and no effect on ventricular function or heart rate variability. An association of LD-CT with major CV events was found in 4/6 studies. This included MI (HR = 1.7 [1.2–2.3]), stroke (OR = 4.36 [1.60–11.90] for LDC between 6 and 10 mg/day), mortality (HR = 2.03 [1.25-3.32]) and a composite index of CV events (in the group of rheumatoid factor positive RA, HR = 2.21 [1.22–4.00]). Two studies did not find any significant association between LD-CT exposure and mortality (OR = 2.25 [0.29–102.5]) or a composite index of CV events (OR = 1.3 [0.8–2.0]). Conclusion Although the literature review showed poor association between LDC exposure and CV risk factors, a trend of increasing major CV events was identified.

Common and different genetic background for rheumatoid arthritis and coeliac disease

Recent genome-wide association studies (GWAS) have revealed genetic risk factors in autoimmune and inflammatory disorders. Several of the associated genes and underlying pathways are shared by various autoimmune diseases. Rheumatoid arthritis (RA) and coeliac disease (CD) are two autoimmune disorders which have commonalities in their pathogenesis. We aimed to replicate known RA loci in a Dutch RA population, and to investigate whether the effect of known RA and CD risk factors generalize across the two diseases. We selected all loci associated to either RA or CD in a GWAS and confirmed in an independent cohort, with a combined P-value cut-off P < 5 x 10(-6). We genotyped 11 RA and 11 CD loci in 1368 RA patients, 795 CD patients and 1683 Dutch controls. We combined our results in a meta-analysis with UK GWAS on RA (1860 cases; 2938 controls) and CD (767 cases; 1422 controls). In the Dutch RA cohort, the PTPN22 and IL2/IL21 variants showed convincing association (P = 3.4 x 10(-12) and P = 2.8 x 10(-4), respectively). Association of RA with the known CD risk variant in the SH2B3 was also observed, predominantly in the subgroup of rheumatoid factor-positive RA patients (P = 0.0055). In a meta-analysis of Dutch and UK data sets, shared association with six loci (TNFAIP3, IL2/IL21, SH2B3, LPP, MMEL1/TNFRSF14 and PFKFB3/PRKCQ) was observed in both RA and CD cohorts. We confirmed two known loci and identified four novel ones for shared CD-RA genetic risk. Most of the shared loci further emphasize a role for adaptive and innate immunity in these diseases.

Is birthweight associated with risk of rheumatoid arthritis? Data from a large cohort study

Objectives:The “fetal origins of adult disease” hypothesis suggests the uterine environment can influence the susceptibility of a fetus to future disease. We examine whether the fetal environment, as reflected by...

Defective proliferative capacity and accelerated telomeric loss of hematopoietic progenitor cells in rheumatoid arthritis

In rheumatoid arthritis (RA), telomeres of lymphoid and myeloid cells are age-inappropriately shortened, suggesting excessive turnover of hematopoietic precursor cells (HPCs). The purpose of this study was to examine the functional competence (proliferative capacity, maintenance of telomeric reserve) of CD34+ HPCs in RA. Frequencies of peripheral blood CD34+,CD45+ HPCs from 63 rheumatoid factor-positive RA patients and 48 controls matched for age, sex, and ethnicity were measured by flow cytometry. Proliferative burst, cell cycle dynamics, and induction of lineage-restricted receptors were tested in purified CD34+ HPCs after stimulation with early hematopoietins. Telomere sequences were quantified by real-time polymerase chain reaction. HPC functions were correlated with the duration, activity, and severity of RA as well as its treatment. In healthy donors, CD34+ HPCs accounted for 0.05% of nucleated cells; their numbers were strictly age dependent and declined at a rate of 1.3% per year. In RA patients, CD34+ HPC frequencies were age-independently reduced to 0.03%. Upon growth factor stimulation, control HPCs passed through 5 replication cycles over 4 days. In contrast, RA-derived HPCs completed only 3 generations. Telomeres of RA CD34+ HPCs were age-inappropriately shortened by 1,600 bp. All HPC defects were independent of disease duration, disease activity, and smoking status, and were present to the same degree in untreated patients. In RA, circulating bone marrow-derived progenitor cells were diminished, and concentrations stagnated at levels typical of those in old control subjects. HPCs from RA patients displayed growth factor nonresponsiveness and sluggish cell cycle progression; marked telomere shortening indicated proliferative stress-induced senescence. Defective HPC function independent of disease activity markers suggests bone marrow failure as a potential pathogenic factor in RA.

The Diagnostic Value of N-Acetyl-β-D-Glucosaminidase and Microalbumin Concentrations in Rheumatoid Arthritis

The Diagnostic Value of N-Acetyl-β-D-Glucosaminidase and Microalbumin Concentrations in Rheumatoid ArthritisThe purpose of this research was to compare the diagnostic values of laboratory variables, to present quantitative evaluations of the diagnostic sifted test with reference to sensitivity and specificity, the predictive value of the positive and negative test and precision of the test for N-acetyl-β-D-glucosa-minidase (NAG), microalbumin, rheumatoid factor (RF), Creactive protein (CRP), DAS 28 index, in early diagnosis of untreated rheumatoid arthritis (RA), and to define the effect of untreated rheumatoid arthritis on glomerular and tubular function. Using a colorimetric assay for the determination of Nacetyl-β-D-glucosaminidase and an immunoturbidimetric assay for the determination of urinary albumin, the samples of serum and urine have been examined in 70 participants (35 RA who were not treated, 35 healthy controls). RF was defined with the test for agglutination (Latex RF test) in the same participants. Out of 35 examined patients with RA, in 13 we found the presence of NAG enzymuria (sensitivity of the test 37.14%), while microalbuminuria appeared in 4 patients (sensitivity of the test 11.42%). RF appeared in 17 patients (sensitivity of the test 48.57%). Four patients were NAG and RF positive, while 3 patients were microalbuminuria and RF positive. Among 18 RF negative patients, 9 patients were NAG positive, and 1 patient presented with microalbuminuria. Among 17 RF positive RA, the presence of NAG was found in 4 patients, and the presence of microalbuminuria in 3 patients. Among 18 RF negative RA, NAG enzymuria appeared in 9 patients. Microalbuminuria was present in 1 patient. In the healthy control group, 8 patients were NAG positive, 2 patients were positive for microalbuminuria. RF appeared in 2 patients. NAG has higher sensitivity than microalbuminuria in the detection of asymptomatic renal lesions in untreated RA.

Complexity of a complex disease; understanding genes, environment and immunity in rheumatoid arthritis development

Rheumatoid arthritis (RA) is a severe and common inflammatory disease with unclear etiology, but is likely to be precipitated and modulated by complex interactions between genetic and environmental factors. Efficient prevention or cure of RA has not yet been developed. Numerous attempts to understand the disease mechanisms and to suggest preventive measures have not been successful. Lately, defining major subtypes of RA by the presence of autoantibodies has been very productive when studying genetic and environmental risk factors for RA. The most replicated risk factors for RA are variations in the HLA-DRB1 gene and smoking and there is also evidence that there is a dose response relationship (i.e., greater number of cigarettes and longer duration of smoking are associated with increased risk of RA). However, these risk factors as well as their interaction have mainly been associated with anticitrullinated peptide antibodies and/or rheumatoid factor positive RA. More research is needed to identify the env...

Recommendations from the Community Oriented Program for Control of Rheumatic Disease for data collection for the measurement and monitoring of health in developing countries

The history of the World Health Organization-International League of Associations for Rheumatology Community Oriented Program for Control of Rheumatic Disease (COPCORD) for developing countries is described. Due to lack of funding and manpower, the COPCORD concept is designed in three stages for execution. Stage I is a community-based epidemiology of rheumatism in three phases by rheumatologist but non-epidemiologist to save time, money, and costs. Stage II is education of treatment of rheumatism. Stage III is the identification of environmental and genetic risk factors of musculoskeletal disorders to prevent or minimize rheumatism. Since 1980, COPCORD has collected valid community-based epidemiological data, which are published in 42 papers since 1985 in various international rheumatology journals. The publications were from 19 developing countries in the Asia Pacific region, South America, Europe, and Africa. Stage II education is deemed to be more appropriate handled by allied rheumatology health professionals. Low back pain, osteoarthritis, osteoporosis, and rheumatoid arthritis (RA) are the priority. The projected prevalence of RA in >4 billion people in countries of the South are between 8 and 12 million patients and urgently require adequate control. After 5-15 years, the consequences of RA are disability, reduced productivity, loss of career and income, lowered quality of life, and early mortality notwithstanding existing therapy. The application of the Biologic DMARDs in RA in the Third World for reasons of treatment costs from $15,000 to $25,000 per patient per year is not feasible. The majority of the Third World population has an income of less than US$1.00 per day to less than US$2,000.00 per capita. The COPCORD has designed and applied successfully the step-down bridge guidelines of intravenous and oral combination of five generic immunosuppressants in prospective observational studies of rheumatoid factor positive RA in Indonesia, China, and Iran. Recommendations of the COPCORD stages are submitted.

Development of sarcoidosis in etanercept-treated rheumatoid arthritis patients

We report two rheumatoid arthritis patients developing sarcoidosis possibly induced by etanercept. Both women, aged 46 and 53, had erosive, rheumatoid-factor-positive rheumatoid arthritis (RA) for 7 and 6 years, respectively. The eldest had received infliximab for over a year with good response, which was stopped because of a perfusion reaction. She developed a cough and dyspnea after 6 months of etanercept treatment. The other developed erythema nodosum and a plaque lesion on the right arm after 1 year of etanercept. Imaging showed, in both cases, mediastinal adenopathies. Biopsies were compatible with sarcoidosis. Etanercept withdrawal led to a complete remission. Recently, there have been reports of noninfectious granulomatous syndromes in patients receiving etanercept for a variety of diseases. In our cases, the temporal association with etanercept therapy and the complete remission after suspension of etanercept suggest a triggering role of this agent. Possible mechanisms of action and supporting evidence are discussed.

Cerebral vasculitis in a patient with rheumatoid arthritis

Inflammatory vasculitis of the central nervous system is exceedingly rare in patients with rheumatoid arthritis (RA). The symptoms may be misleading. Most of the reported cases occurred in males with long-standing, nodular, destructive, rheumatoid factor-positive disease. Severe constitutional symptoms and prominent extraarticular manifestations of vasculitis were usually present. We report a case of cerebral vasculitis in a 59-year-old woman with a 20-year history of destructive rheumatoid factor-positive RA that was well controlled by methotrexate. Headache that was unresponsive to symptomatic treatment developed abruptly, together with gait disorders. Magnetic resonance imaging of the brain showed dot-like areas of high-signal in a periventricular subcortical distribution on both sides. Magnetic resonance angiography visualized a long tight stenosis of the right internal carotid artery and a string-of-beads stenosis of the left internal carotid artery suggesting vasculitis. Pulse therapy with methylprednisolone (1 g/d for 3 days) and cyclophosphamide (1 g) once a month ensured resolution of the neurological symptoms and laboratory evidence of inflammation. There was no evidence of a relapse at last follow-up after 5 months. Cerebral vasculitis is usually treated with monthly glucocorticoid and cyclophosphamide boluses separated by continuous glucocorticoid therapy. TNFα antagonists may be effective in patients who fail to respond to conventional treatment. However, other vasculitides such as giant cell arteritis and Wegener's granulomatosis must be ruled out, as they are refractory to TNFα antagonist therapy.

Spondyloarthropathy: An Independent Risk Factor for Kidney Stones

To better stratify risk and to verify previous prevalence reports, we conducted a retrospective cohort study comparing the lifetime incidence of nephrolithiasis in patients with spondyloarthropathies (SpA) and rheumatoid arthritis (RA). Patients with SpA or rheumatoid factor-positive RA were identified from the rheumatology clinics of two Veterans Affairs hospitals and the University of Minnesota. Among them, 168 were confirmed to meet the American College of Rheumatology criteria and gave informed consent to participation. They were sent a survey regarding their rheumatologic diagnosis, coexistent conditions, medications, and history of kidney stones. Of the total, 143 patients responded and met the criteria for analysis. Rheumatoid arthritis patients were age and sex matched with SpA patients as controls. Populations were similar in all categories except that RA patients were more likely to have used prednisone (P < 0.001), bisphosphonates (P < 0.001), and calcium supplementation (P = 0.03). Kidney stones were reported by 23 (29.11%) of the 79 SpA patients compared with 8 (12.5%) of the 64 RA patients (chi (2) = 5.75; P = 0.025). Subgroup analysis of self-reporting stone history in 85 patients was found to be reliable on imaging review (sensitivity 82%; specificity 100%). Self-reporting of kidney stones by patients is a reliable measure. Despite adjusting for medication use and matching two similar arthritic populations, patients with SpA had a higher incidence of kidney stones than those with RA. This finding suggests that SpA is an independent risk factor for nephrolithiasis. Future studies will evaluate urinary risk factors and polymorphisms in the ANKH gene that may predispose to stone formation in this high-risk group.

The PTPN22 R620W polymorphism associates with RF positive rheumatoid arthritis in a dose-dependent manner but not with HLA-SE status

We have recently described the association between rheumatoid arthritis and a coding single-nucleotide polymorphism in the intracellular protein tyrosine phosphatase, PTPN22. The disease-associated polymorphism, 1858 C/T (rs2476601), encodes an amino-acid change (R620W) in one of four SH3 domain binding sites in the PTPN22 molecule. We have now extended our initial studies to address three questions: (1) Is the association with rheumatoid arthritis limited to rheumatoid factor (RF) positive disease? (2) Does homozygosity for PTPN22 R620W substantially increase disease susceptibility? (3) Is there an interaction between PTPN22 and the rheumatoid arthritis (RA)-associated HLA-DRB1 shared epitope alleles? A total of 1413 Caucasian rheumatoid arthritis patients and 1401 Caucasian controls were genotyped. The results support the view that PTPN22 was strongly and preferentially associated with RF positive disease (OR=1.75, 95% CI 1.46-2.10, P=1.3 x 10(-9)). The PTPN22 risk allele was not significantly associated with RF negative disease (OR=1.19, 95% CI 0.92-1.53, P=0.18), although a very weak association cannot be completely excluded. There was a strong dose effect on disease risk; two copies of the PTPN22 R620W allele more than doubles the risk for RF positive RA (OR=4.57, 95% CI 2.35-8.89). There was no evidence of a genetic association between PTPN22 and HLA susceptibility alleles.

The advanced glycation end product pentosidine correlates to IL-6 and other relevant inflammatory markers in rheumatoid arthritis

Oxidative stress and inflammatory processes accelerate the formation of advanced glycation end products (AGE), e.g. of pentosidine. The aim of this study was to investigate the relationships between levels of pentosidine in serum and synovial fluid, proinflammatory cytokines, other markers of inflammatory activity, and the state of radiologically visible bone destruction in patients with rheumatoid arthritis (RA). One hundred thirty-three nondiabetic RA patients and 56 age-matched, healthy subjects were included. Serum and synovial fluid pentosidine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and rheumatoid factor levels were determined. In 30 patients, the proinflammatory cytokines interleukin (IL)-1beta, IL-6, and TNF-alpha and the soluble receptors sIL-2R, sIL-6R, sTNF-alpha, and RI/RII were also measured. Serum levels of pentosidine were on average significantly higher in RA patients than in healthy subjects and correlated significantly to ESR, CRP, and serum levels of IL-6. Serum and synovial fluid pentosidine did not show any differences. Rheumatoid factor-positive RA patients had higher pentosidine levels in the synovial fluid than rheumatoid factor-negative patients. Correlations could not be found between pentosidine and the other cytokines or cytokine receptors measured. The binding of AGE on cell receptors induces activation of nuclear factor kappa B, resulting in enhanced synthesis of proinflammatory cytokines. Moreover, AGE generation may also lead to the formation of new, immunologically relevant epitopes at synovial proteins. Both mechanisms could contribute to initiation and perpetuation of the inflammatory and destructive processes in RA.

Class II MHC alleles in rheumatoid arthritis in Tamilnadu, India: is there an association?

Rheumatoid arthritis (RA) was reported to be associated with class II MHC alleles in different ethnic populations. A similar study was undertaken to determine the association of class II MHC with RA patients of Tamilnadu (Tamil-speaking Hindus), India. Thirty patients with RA and 39 healthy controls were included. Polymorphic second exons of the DRB1, DQA1, and DQB1 genes were amplified and subjected to SSOP typing. No allele was found to be significantly associated with RA. However DRB1*11 (P = 0.01) and DQB1*0302 (P = 0.02) were significantly associated with rheumatoid factor-positive RA patients. (All the DRB1*11-positive RA patients had either *04 or *10 allele as their second allele. This study is first of its kind in this population.

A variant of HLA–DR4 determines susceptibility to rheumatoid arthritis in a subset of Israeli Jews

HLA-DR4 is associated with risk for developing rheumatoid arthritis (RA) in most populations. In Israeli Jews, in whom the Dw10 subtype of DR4 predominates, no association of RA with DR4 has been found. The inability to detect an association could be due to the high frequency of DR4-Dw10. We used DNA typing with amplification by the polymerase chain reaction and dot-blotting with allele-specific oligonucleotides to determine DR4 variants in 131 Jewish RA patients living in Israel and 134 controls. In both Ashkenazi Jews and non-Ashkenazi Jews, the rare variant Dw15 (previously identified in Japanese populations and in Japanese patients with RA) was found to be the main allele associated with the risk of developing RA (relative risk = 9.2, corrected P less than 0.001). However, this low-frequency allele could be responsible for susceptibility in only 11.5% of the patients. Susceptibility for rheumatoid factor-positive RA was associated with Dw4 and Dw15; the risk for rheumatoid factor-negative RA was associated only with Dw14. The distribution of the HLA-DQ alleles associated with DR4 showed that more than half of the RA patients with Dw15 also had HLA-DQw2. The frequencies of DQw7 and DQw8 were not different in RA patients compared with controls. The results suggest that, as in other populations, susceptibility for the development of RA in Israeli Jews is associated with DRB1 locus alleles of the DR4 group.

HLA-D and IA antigens in rheumatoid arthritis and systemic lupus erythematosus

The HLA-D region in the HLA chromosomal complex is concerned with cellular interactions and regulation of the immune response. Rheumatoid arthritis (RA) has been found to be associated with one of the HLA-D antigens. In two separate studies from this laboratory it was found that HLA-Dw4 was more frequent in RA patients than in normal controls. The patients were Caucasians suffering from erosive, rheumatoid factor positive RA. Combined results of the two studies showed HLA-Dw4 to be present in 52% of the 130 patients, compared to 13% in 119 controls (P less than 10(-6). Ia antigens were determined serologically in isolated B cells. The antigen Ia4, associated with HLA-Dw4, was increased in RA patients (70%), compared to normal controls (28%). In SLE, typing was difficult because of fragility of the B cells. Preliminary results in 14 SLE patients suggested that Ia4 was also increased in this disease. It seems likely that these associations are a reflection of genetic factors related to the immune response involved in the pathogenesis of RA and perhaps also of SLE.