Value of isolated IgA anti-ß2 -glycoprotein I positivity in the diagnosis of the antiphospholipid syndrome.

OBJECTIVE: To examine the prevalence of isolated IgA anti-ß2 -glycoprotein I (anti-ß2 GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of ß2 GPI, with clinical manifestations of the antiphospholipid syndrome (APS) in 3 patient groups and to evaluate the pathogenicity of IgA anti-ß2 GPI in a mouse model of thrombosis. METHODS: Patients with systemic lupus erythematosus (SLE) from a multiethnic, multicenter cohort (LUpus in MInorities, NAture versus nurture [LUMINA]) (n = 558), patients with SLE from the Hopkins Lupus Cohort (n = 215), and serum samples referred to the Antiphospholipid Standardization Laboratory (APLS) (n = 5,098) were evaluated. IgA anti-ß2 GPI titers and binding to domain IV/V of ß2 GPI were examined by enzyme-linked immunosorbent assay (ELISA). CD1 mice were inoculated with purified IgA anti-ß2 GPI antibodies, and surgical procedures and ELISAs were performed to evaluate thrombus development and tissue factor (TF) activity. RESULTS: A total of 198 patients were found to be positive for IgA anti-ß2 GPI isotype, and 57 patients were positive exclusively for IgA anti-ß2 GPI antibodies. Of these, 13 of 23 patients (56.5%) in the LUMINA cohort, 17 of 17 patients (100%) in the Hopkins cohort, and 10 of 17 patients (58.9%) referred to APLS had at least one APS-related clinical manifestation. Fifty-four percent of all the IgA anti-ß2 GPI-positive serum samples reacted with domain IV/V of anti-ß2 GPI, and 77% of those had clinical features of APS. Isolated IgA anti-ß2 GPI positivity was associated with an increased risk of arterial thrombosis (P < 0.001), venous thrombosis (P = 0.015), and all thrombosis (P < 0.001). The association between isolated IgA anti-ß2 GPI and arterial thrombosis (P = 0.0003) and all thrombosis (P = 0.0003) remained significant after adjusting for other risk factors for thrombosis. In vivo mouse studies demonstrated that IgA anti-ß2 GPI antibodies induced significantly larger thrombi and higher TF levels compared to controls. CONCLUSION: Isolated IgA anti-ß2 GPI-positive titers may identify additional patients with clinical features of APS. Testing for these antibodies when other antiphospholipid tests are negative and APS is suspected is recommended. IgA anti-ß2 GPI antibodies directed to domain IV/V of ß2 GPI represent an important subgroup of clinically relevant antiphospholipids.

Subtypes of HLA-B27: history and implications in the pathogenesis of ankylosing spondylitis.

HLA-B27 represents a family of 38 closely related cell surface proteins (encoded by the alleles HLA-B*2701-39) called subtypes of HLA-B27, most of which have evolved from the ubiquitous HLA-B*2705 (specifically the B*27052 allele). HLA-B27 subtypes are largely characterized by nucleotide substitutions (mostly nonsynonymous) in exons 2 and 3 which encode alpha1 and alpha2 domains ofthe peptide binding groove respectively. Table 1 shows the description of sequences of HLA-B27 allele sequences. The subtypes could have arisen from B*2705 by point mutation (B*2703, B*2709, B*2704), gene conversion (B*2701, B*2702, B*2708) and reciprocal recombination (B*2707) B*2706 could have arisen by interlocus gene conversion. Studies from different parts of the world reveal differences in the population distribution.

What factors relate to job satisfaction among rheumatologists?

BACKGROUND: A severe shortage of practicing rheumatologists in the workforce is predicted over the next 2 decades. Identification of factors impacting job satisfaction will be needed to design interventional strategies for physician retention. OBJECTIVE: To examine predictors of job satisfaction among rheumatologists. METHODS: A cross-sectional survey was conducted among rheumatologists from the American College of Rheumatology directory with a portion of this designed to examine their job satisfaction. Questions regarding demographics, practice setting and job satisfaction, emotional exhaustion, and personal accomplishment based from the Maslach Burnout Inventory were included. Also included was a rank item to prioritize perceived changes that would improve job satisfaction. The response rate was 30% (N = 285) and 236 were analyzed. Data were primarily analyzed by the independent samples chi2 test. RESULTS: Physician demographics: mean age: 51 years, 76% were male, 27% were full time academicians, and 24% in solo practice. Significant differences (P < 0.04) between the "high" satisfaction versus "very good" and "low" satisfaction groups includes increased age and solo practice, which were associated with "high" satisfaction. Lower job satisfaction rating correlated with items rating emotional exhaustion (r(s) = -0.43) and better satisfaction with personal accomplishment (r(s) = 0.41, P < 0.001 for both). Priority ranking revealed that "better reimbursement for patient care" and "less administrative/business effort" were the most frequently reported items cited to improve job satisfaction. CONCLUSIONS: Measures to improve job satisfaction may promote physician retention as a means of addressing the predicted workforce shortage.

Therapy insight: the changing spectrum of rheumatic disease in HIV infection.

HIV infection and AIDS have protean and multisystem manifestations throughout the various stages of infection. Progression from HIV infection to AIDS is associated with a gradual loss of immunocompetence and the occurrence of opportunistic infections and malignancies; it is also associated with immune dysregulation and persistent, prolonged immune activation that leads to autoimmune phenomena such as vasculitis and serological abnormalities. In people who are infected with HIV, the recognition of autoinflammatory disorders, their differentiation from infections or lymphoproliferative malignancies and their treatment using potentially immunosuppressive drugs is a challenging clinical scenario. The spectrum of rheumatologic diseases reported in HIV-infected individuals has changed dramatically since the introduction of highly active antiretroviral therapy in 1995. Complications such as metabolic abnormalities, osteoporosis, and immune restoration inflammatory syndrome have emerged.

Factors that impact decision making among rheumatologists in the initiation of treatment for hypertension in rheumatoid arthritis.

BACKGROUND: Increased risks of morbidity and mortality from cardiovascular (CV) events are reported in patients with rheumatoid arthritis (RA). Recent reviews recommend aggressive treatment of modifiable CV risk factors, including systemic hypertension (HTN). OBJECTIVES: We examined possible contributory factors influencing HTN treatment among RA patients by rheumatologists. METHODS: We conducted a cross-sectional 36-item survey of randomly chosen rheumatologists from the American College of Rheumatology directory collecting the rheumatologists' demographics, practice, and perceptions regarding HTN treatment in their RA patients. Our response variable was initiation of HTN treatment. Independent variables were derived from responses to the survey, and data were analyzed using bivariate analysis and logistic regression. RESULTS: Of 938 rheumatologists surveyed, 285 (30%) responded, 236 were subsequently analyzed. Respondents' mean age was 52.8 years; 75% were male and most were white (83%). Respondents reported routinely screening for HTN (92.8%), and initiating treatment for HTN (31%) in RA patients. Rheumatologists who believed that their RA patients did not have adequate visits with their primary care providers (PCP) were 2.2 times as likely to initiate treatment for HTN (41.1% vs. 24.3%; P = 0.006). Conversely, 33% of rheumatologists who did not routinely initiate treatment for HTN in their RA patients also did not believe patient access to PCP care was adequate. No associations were observed between initiation of HTN treatment and physician demographic or practice items. CONCLUSION: The need for more effective minimization of CV risks in RA patients should prompt rheumatologists to consider a revision of routine practice standards to include treatment of uncontrolled HTN or promotion of improved communication with their PCPs.