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P-glycoprotein (P-gp)-mediated efflux of corticosteroids (CS) may contribute to treatment unresponsiveness in Lupus Nephritis (LN) patients. Tacrolimus is a P-gp inhibitor and hence, may overcome this resistance. We aimed to study the response to tacrolimus, along with the expression and function of P-gp on peripheral blood lymphocytes (PBL) in patients with refractory and relapsing proliferative Lupus Nephritis. We enrolled 12 refractory/relapsing LN patients and treated them with corticosteroids and tacrolimus for 6 months. Expression and function of P-gp on PBL was measured by flow cytometry (as relative fluorescence index, RFI and Rhodamine dye efflux assay) before and 3 months after tacrolimus therapy. Renal response was assessed according to ACR response criteria after 3 and 6 months of tacrolimus therapy. 8 out of 12 refractory/relapsing LN patients achieved renal response (5 partial response, PR and 3 complete responses, CR) as early as 3 months, and 11 patients achieved renal response (7 PR and 4 CR) at 6 months from start of tacrolimus therapy. Proteinuria decreased from median urine protein creatinine ratio (UPCR) of 2.80 (2.00-3.40) at baseline to 1.20 (0.66-1.73) at 3 months (p 0.001) and to 0.80 (0.19-1.30) at 6 months (p 0.01). There was significant decrease in P-gp expression [RFI, 3.33 (2.87-4.97) vs 2.03 (1.25-3.86), p 0.05) and P-gp function (RFI, 55.7 (29.7-84.1) vs 26.8 (16.1-37.0), p 0.01) after 3 months of tacrolimus therapy. Tacrolimus achieves renal response in refractory/relapsing proliferative LN patients which may be partly related to overcoming P-glycoprotein mediated treatment unresponsiveness.

Introduction T-helper 17 (Th17) cells and T-regulatory (Treg) cells have been suggested to play pathogenic roles in lupus nephritis. The in vivo effects of current therapies for lupus nephritis (LN) on these cells have not been adequately studied. Methods We conducted a prospective observational study among patients with active proliferative lupus nephritis (LN) who received Eurolupus induction therapy and assessed them as per the European League Against Rheumatism criteria for renal response. Peripheral circulatory Th17 and Treg cell numbers were enumerated at start of therapy, at 3 and 6 months follow-up periods using flow cytometry. Baseline values were compared with inactive lupus patients (iSLE) and healthy controls (HC). Results Thirty patients with LN, 20 iSLE and 22 HC were enrolled into the study. In LN, Th17 frequency was significantly higher compared to HC, and Treg frequency significantly lower compared to both iSLE and HC. Nineteen patients fulfilled criteria for response (partial or complete) at 6 months. Responder group showed a significant decline in Th17 frequency and an increasing trend in Treg frequency compared to baseline after 6 months of therapy. Conclusion Circulating Th17 cells were significantly raised in patients with active proliferative LN and showed a significant reduction in responder patients following therapy.

Multiple myeloma can rarely mimic seronegative rheumatoid arthritis (RA). We report a 55-year-old woman who presented with longstanding deforming polyarthritis with extensive subcutaneous nodules, tenosynovitis, anti-cyclic citrullinated peptide positivity and mononeuritis multiplex. Even though the clinical picture was consistent with seropositive RA, the absence of bone erosion or joint space narrowing on hand and knee radiographs led us to question the diagnosis of RA. Further investigation revealed a diagnosis of multiple myeloma with cutaneous amyloid deposits, based on serum immunofixation, bone marrow aspiration and biopsy of a subcutaneous nodule. The only clue to suspect myeloma from the basic investigations and clinical examination was mild hypercalcemia. This case serves to reiterate the need to maintain a heightened suspicion for other diagnoses even when RA appears most likely.

AIM To assess the frequency and risk factors of asymptomatic vertebral fractures in inflammatory myositis. PATIENTS AND METHODS Dorsal and lumbar spine lateral radiographs were taken for adults with inflammatory myositis and scored using Genant's semi-quantitative technique. Demographic data, weight, height, postmenopausal status, duration of corticosteroid use, drug intake, co-morbidities and past history of fractures were recorded. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry (DEXA). Myositis Damage Index (MDI) was also assessed. All results are expressed in median and interquartile range. RESULTS One hundred patients (82 female) with myositis of median age 35.5 (28.5-46) years and disease duration 3.0 (1.81-8.0) years were studied. Thirty-five patients had adult dermatomyositis (DM), 26 polymyositis, 31 connective tissue disease-associated myositis and eight had juvenile onset myositis. Seventeen were postmenopausal women. Forty-six patients had asymptomatic vertebral fractures and 19 had more than one fracture. Half the fractures occurred in those with disease duration of

Summary An increased expansion of T helper type 17 (Th17) cells in the synovium has been shown to play a key role in cartilage and bone destruction in rheumatoid arthritis (RA). Because the correlation of the peripheral blood helper T cell subsets and various inflammatory cytokines with the magnetic resonance imaging (MRI)-based parameters have not been studied adequately to date, we sought to look for the same in this study. RA patients with disease duration less than 36 months, disease-modifying anti-rheumatic drugs (DMARDs) and steroid-naive, were recruited. MRI of the dominant hand and wrist was performed using a 0·2 Tesla MRI machine. Peripheral blood Th1 and Th17 were enumerated by flow cytometry and serum interleukin (IL)-6 and IL-17 by enzyme-linked immunosorbent assay (ELISA). Forty consecutive seropositive RA patients [33 females, mean disease duration 12·2 months, mean disease activity score (DAS)28 = 4·4] were included. MRI revealed erosions in 80% of these subjects. On subgroup analysis, prevalence of erosions (94 versus 68%) as well as mean erosion score (11·5 ± 18·9 versus 3·5 ± 6·0) were significantly higher in established RA (13–36 months' duration) compared to early RA (0–12 months). The median peripheral blood Th17 frequencies were significantly higher in patients (1·4%) compared to healthy controls (0·7%) and had a strong negative correlation with MRI parameters of erosion and osteitis as well as with DAS28 in the established RA subgroup. The frequency of peripheral blood Th17 subset was significantly expanded in established RA which correlated inversely with disease activity as well as MRI based erosions and osteitis.

Opportunistic infections pose a significant problem in patients receiving immunosuppressive therapy for autoimmune diseases. We present a case of a woman with polymyositis refractory to high-dose steroid and methotrexate, as a consequence of which she developed miliary tuberculosis. Her myositis went into remission after initiation of antitubercular therapy, in spite of bringing down the intensity of immunosuppression. This is the first reported case of myositis undergoing remission after treating intercurrent infection, and illustrates the complex relationship between autoimmune disease and host response to infection.