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Objective: Autoantibodies against citrullinated peptide antigens (ACPA) are routinely determined to diagnose rheumatoid arthritis (RA) and are predictive of a more severe course of the disease. We here set out to address an involvement of ACPA in the pathogenesis of RA and investigated the recognition pattern of antibodies against 2 citrullinated antigens in more detail., Methods: The sera of 77 patients fulfilling the American College of Rheumatology criteria for RA were analyzed for subclass titers of anti-mutated citrullinated vimentin (MCV) and anticyclic citrullinated peptide (CCP) antibodies by combining subclass specific detection antibodies with commercially available CCP and MCV ELISA plates. Cross-reactivities between anti-MCV and anti-CCP antibodies were detected using a sequential ELISA system., Results: IgG1, IgG3, and IgG4 titers among anti-MCV and anti-CCP antibodies correlated significantly. Cross-reactivity of MCV-specific antibodies against CCP could be detected in 8 of 16 patients' sera; however, cross-binding of MCV-specific IgG4 was weaker compared to total IgG., Conclusion: The inherent capacity of IgG4 to exchange F(ab) arms provides insight into the anti-MCV antibody diversity and suggests a classification of ACPA positive patients into broad and narrow responders.

Objective: To define the relationship between bone growth (syndesmophytes) and bone loss (osteoporosis) in ankylosing spondylitis (AS)., Methods: Bone mineral density (BMD) at the spine, hip, and radius was measured by dual-energy x-ray absorptiometry (DEXA), dual-energy quantitative computed tomography (DEQCT), and peripheral quantitative computed tomography (pQCT) in 103 patients with AS. Radiographs of the lumbar spine were used to detect syndesmophytes. Patients were divided in 3 groups according to disease duration., Results: Osteopenia at the hip and spine was found by DEXA in 56% and 41%, respectively, of the patients with disease duration < 5 years (n = 27), with an additional 11% and 15% having osteoporosis. In patients with a longer disease duration, > 10 years (n = 28), 29% were osteoporotic at the hip and only 4% at the lumbar spine. In contrast, using spinal DEQCT, 59% of patients with early disease were found to be osteopenic; 36% of patients with long-standing disease were osteopenic and 18% were osteoporotic. More than half the patients (55%) had syndesmophytes (n = 55). With spinal DEQCT there were more patients with syndesmophytes (63%) in the group with reduced bone density than in the group without (45%). This was similar with DEXA measurements at the hip, where 31% compared to 14% had osteoporosis, respectively. Osteocalcin was elevated in 34% of patients, but was not associated with disease activity or BMD., Conclusion: The majority of patients with AS had reduced bone density. The method of bone density measurement is critical and should be different depending on disease duration. The finding that more patients with syndesmophytes had reduced bone density than those without suggests that bone growth and bone loss occur in parallel, and the role of inflammation in this process warrants further investigation.