Objective. The main genetic risk factor for rheumatoid arthritis (RA), the HLA region, has been known for 25 years. Previous research has demonstrated, within the RA population, an association between HLA-DRB1 alleles carrying the shared epitope (SE) and antibodies directed against cyclic citrullinated peptides (anti-CCP antibodies). We undertook this study to make the first comparison of SE allele frequencies in the healthy population with those in RA patients who do or do not harbor anti-CCP antibodies.Methods. HLA-DRB1 typing was performed in 408 RA patients from the Leiden Early Arthritis Clinic (the Leiden EAC; a Dutch population-based inception cohort in which disease course was followed up over time), in 423 healthy Dutch controls, and in 720 affected members of 341 US multiplex (sibpair) families of Caucasian origin from the North American RA Consortium (NARAC) with well-established disease and fulfilling the American College of Rheumatology classification criteria for RA. The presence of anti-CCP antibodies was determined by enzyme-linked immunosorbent assay.Results. For the Leiden EAC, the odds ratio (OR) describing the association of 2 copies of the SE allele with anti-CCP positivity (using no copies of the SE allele in the healthy control group as the referent) was 11.79 (P < 0.0001), while the OR for 1 SE allele was 4.37 (P < 0.0001). No association with the SE was observed in the Dutch anti-CCP-negative RA patients. For the NARAC families, linkage and association analysis revealed the SE to be associated only with anti-CCPpositive disease and not with anti-CCP-negative disease. Stratified analyses indicated that anti-CCP antibodies primarily mediated association of the SE with joint damage or disease persistence.Conclusion. HLA-DRB1 alleles encoding the SE are specific for disease characterized by antibodies to citrullinated peptides, indicating that these alleles do not associate with RA as such, but rather with a particular phenotype.

Objective: The objective of this retrospective study of non-inflammatory rheumatic disease patients was to investigate if the individuals clinically identified with muscular hypertonicity (MHT) had increased clinical manifestations compared with those of age-and gender-matched patients with the same disorders. Material and Methods:The MHT status was clinically identified in the rheumatologist's myofascial protocol examination as relatively increased passive resistance of relaxed muscle on a slow gentle stretch. Clinical and laboratory data were abstracted on a pre-coded form, including symptom and physical examination features, serum assays, and medications.Results: The 19 MHT cases complained of greater subjective stiffness (p=0.010) and tiredness (p=0.018) at initial encounters and increased aching pain (p=0.049) and were prescribed more (p=0.003) mild narcotic analgesics than the 19 comparison patients. The cases had higher (p=0.027) serum creatine kinase levels, and patients with diffuse MHT had greater frequency of heavy (30+pack-years) cigarette smoking (p=0.002) than comparison subjects. Narcotic usage was also greater in cases with diffuse involvement.Conclusion: Non-inflammatory rheumatic disease patients with MHT had an overall similar profile as that of comparison patients but had greater musculoskeletal complaints, and those with diffuse involvement had greater narcotic usage. Further research, including quantitative measurements of muscle stiffness, are required to determine whether MHT is a documented entity associated with increased rheumatological manifestations.

No abstract

No abstract