Thrombotic thrombocytopenic purpura that developed 3 years after systemic lupus erythematosus had remitted with rituximab therapy.

Patients with systemic lupus erythematosus (SLE) occasionally develop thrombotic thrombocytopenic purpura (TTP), which can be fatal. Here, we report a case of TTP developing 3 years after SLE remitted with rituximab (RTX) therapy. A 50-year-old woman was treated with RTX for marked immune thrombocytopenic purpura and autoimmune haemolytic anaemia due to SLE relapse. After induction of remission, she was treated with prednisolone alone without maintenance therapy with RTX. Approximately 3 years later, she was readmitted with marked thrombocytopenia and severe renal dysfunction. On admission, she was diagnosed with TTP for the first time based on severe reduction in a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity and detection of ADAMTS13 inhibitors. CD19+ B cells in the patient's serum increased to 34%, suggesting that B cells had reactivated once the effect of RTX had subsided. The patient was successfully treated with plasmapheresis, glucocorticoid pulse therapy, and RTX. There are no previous reports of newly diagnosed TTP with ADAMTS13 inhibitor production after having achieved remission of SLE with RTX. Therefore, our report also discusses the potential mechanisms of production of new autoantibodies after B-cell depletion therapy.

N-glycan in the variable region of monoclonal ACPA (CCP-Ab1) promotes the exacerbation of experimental arthritis.

OBJECTIVES: The variable region of most ACPA IgG molecules in the serum of RA patients carries N-glycan (N-glycanV). To analyse the pathogenicity of N-glycanV of ACPAs, we analysed the pathogenicity of a monoclonal ACPA, CCP-Ab1, with or without N-glycanV, which had been isolated from a patient with RA. METHODS: CCP-Ab1 with no N-glycosylation site in the variable region (CCP-Ab1 N-rev) was generated, and antigen binding, the effect on in vitro differentiation of osteoclasts from bone marrow mononuclear cells of autoimmune arthritis-prone SKG mice (the cell size of TRAP+ cells and bone resorption capacity) and the in vivo effect on the onset or exacerbation of autoimmune arthritis in SKG mice were evaluated in comparison with glycosylated CCP-Ab1. RESULTS: Amino acid residues in citrullinated peptide (cfc1), which are essential for binding to CCP-Ab1 N-rev and original CCP-Ab1, were almost identical. The size of TRAP+ cells was significantly larger and osteoclast bone resorption capacity was enhanced in the presence of CCP-Ab1, but not with CCP-Ab1 N-rev. This enhancing activity required the sialic acid of the N-glycan and Fc region of CCP-Ab1. CCP-Ab1, but not CCP-Ab1 N-rev, induced the exacerbation of experimental arthritis in the SKG mouse model. CONCLUSIONS: These data showed that N-glycanV was required for promoting osteoclast differentiation and bone resorption activity in both in vitro and in vivo assays. The present study demonstrated the important role of N-glycanV in the exacerbation of experimental arthritis by ACPAs.

The Lipopolysaccharide Mutant Re-LPS Is a Useful Tool for Detecting LPS Contamination in Rheumatoid Synovial Cell Cultures.

INTRODUCTION: Lipopolysaccharide (LPS) contamination of commercially available proteins has seriously impeded research on citrullinated fibrinogen (cit-Fb) in rheumatoid synovial cells (RSCs). METHODS: RSCs obtained from 4 rheumatoid arthritis patients who underwent full knee arthroplasty were cultured, stimulated with cit-Fb, and cytokine expression levels were measured. We then evaluated polymyxin-B (PMB), heat inactivation, and rough (R)-type LPS mutants for rapid detection of LPS contamination. RESULTS: cit-Fb induced expression of CXCL10 and IFNB in RSCs via the toll-like receptor. PMB inhibited cit-Fb-mediated CXCL10 gene expression but not protein expression induced by 20 µg/mL cit-Fb. Heat inactivation did not affect LPS-mediated CXCL10 or IL-6 induction; however, cit-Fb-mediated CXCL10expression was inhibited. Wild-type LPS from Escherichia coli (WT-LPS) strongly induces CXCL10 expression, but induction by Ra-LPS was weak, and induction by Rc- and Re-LPS was minimal. Re-LPS suppression of WT-LPS-mediated CXCL10 induction in RSCs and peripheral blood monocytes (PBMs) was dose dependent. Furthermore, Re-LPS completely suppressed cit-Fb-mediated CXCL10 induction in RSCs and PBMs. CONCLUSION: To easily identify LPS contamination during routine experiments, our results suggest that Re-LPS is a better tool for rapid detection of LPS contamination compared to PMB and heat treatment.

A Case of Granulomatosis with Polyangiitis with Various Breast Lesions as the Initial Symptoms: A Case-Based Review.

A 44-year-old woman presenting with pus-like discharge from the nipples visited our hospital for scleritis. Subcutaneous induration and ulceration were found on her breast. She was diagnosed with granulomatosis with polyangiitis (GPA) considering scleritis, sinusitis, cutaneous granuloma formation, and antiproteinase 3-antineutrophil cytoplasmic antibodies and was successfully treated with glucocorticoids. Fifteen months later, she developed pulmonary consolidation and a right breast nodule. Biopsies of the breast nodule showed granulomatous vasculitis, and she was treated with rituximab. While breast involvement in GPA is rare, unilateral breast mass is a typical clinical feature; thus, GPA should be considered in such cases.