The TTTT B lymphocyte stimulator promoter haplotype is associated with good response to rituximab therapy in seropositive rheumatoid arthritis resistant to tumor necrosis factor blockers.

OBJECTIVE: To investigate the polymorphisms in the promoter region of the B lymphocyte stimulator (BLyS) gene as markers of response to rituximab (RTX) in rheumatoid arthritis (RA). METHODS: The study was first conducted in 152 Italian RA patients and then replicated in an additional 117 RA patients (73 Italian, 44 British). The European League Against Rheumatism response criteria were used to evaluate the response rate at months 4 and 6 after the first cycle of RTX, by means of the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate; patients were classified according to the best response shown between months 4 and 6. BLyS promoter polymorphisms were analyzed by polymerase chain reaction followed by the analysis of the restriction fragments, BLyS promoter haplotypes were analyzed using the expectation-maximization algorithm, and BLyS serum levels were analyzed using enzyme-linked immunosorbent assay. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs). RESULTS: The TTTT BLyS promoter haplotype appeared to be significantly associated with response to RTX only in the subset of seropositive patients (those positive for rheumatoid factor and/or anti-cyclic citrullinated peptide). The replication study confirmed that this association was limited to seropositive RA patients in whom treatment with anti-tumor necrosis factor (anti-TNF) agents had previously failed. In the whole series of seropositive patients in whom anti-TNF agents had previously failed, patients carrying the TTTT BLyS promoter haplotype were more prevalent in good responders (18 of 43 [41.9%]) than in moderate responders (20 of 83 [24.1%]) or in nonresponders (1 of 21 [4.8%]) (for good responders versus nonresponders, OR 14.4 [95% CI 1.77-117.39], P=0.0028). Furthermore, multivariate analysis selected the TTTT BLyS promoter haplotype as an independent marker of good response to RTX (for good responders versus nonresponders, OR 16.2 [95% CI 1.7-152.5], P=0.01; for good responders versus moderate responders and nonresponders combined, OR 3.1 [95% CI 1.2-7.8], P=0.02). The relationship between BLyS polymorphisms and BLyS serum levels remained unclear. CONCLUSION: BLyS promoter genotyping may be suitable for identifying seropositive RA patients who may have a good response to RTX after anti-TNF agents have failed.

Alexithymia and Psychological Distress in Patients With Fibromyalgia and Rheumatic Disease.

BACKGROUND: Fibromyalgia syndrome (FMS) is a chronic rheumatologic disease characterized by widespread musculoskeletal pain and other psychopathological symptoms which have a negative impact on patients' quality of life. FMS is frequently associated with alexithymia, a multidimensional construct characterized by difficulty in identifying feelings (DIF) and verbally communicating them difficulty describing feelings (DDF) and an externally oriented cognitive thinking style (EOT). The aim of the present study was to investigate the relationship between alexithymia, anxious and depressive symptoms and pain perception, in patients with FMS and other rheumatic diseases (RD). METHODS: The sample consisted of 127 participants (M = 25, F = 102; mean age: 51.97; SD: 11.14), of which 48 with FMS, 41 with RD and 38 healthy control group (HC). All groups underwent to a test battery investigating anxiety and depressive symptoms (HADS), pain (VAS; QUID-S/-A) and alexithymia (TAS-20). RESULTS: A high prevalence of alexithymia (TAS ≥ 61) was found in FMS (47.9%) and RD (41.5%) patients, compared to the HC group (2.6%). FMS patients showed significant higher scores than HC on DIF, DDF, EOT, anxiety and depression. The clinical sample, FMS and RD groups combined (n = 89), alexithymic patients (AL, n = 40) exhibited higher scores in pain and psychological distress compared to non-alexithymic patients (N-AL, n = 34). Regression analysis found no relationship between alexithymia and pain in AL, meanwhile pain intensity was predicted by anxiety in N-AL. CONCLUSION: While increasing clinical symptoms (pain intensity and experience, alexithymia, anxiety, and depression) in patients with fibromyalgia or rheumatic diseases, correlations were found on the one side, between alexithymia and psychological distress, on the other side, between pain experience and intensity. Meanwhile, when symptoms of psychological distress and alexithymia were subthreshold, correlations with pain experience and intensity became stronger.