Diagnosis of neuropsychiatry disorder in patients with anti-MDA5 antibody dermatomyositis: A case report.

Anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis (DM) is a rare disease that can be easily misdiagnosed. Anti-MDA5 dermatomyositis is a subtype of DM. It is distinguished by the presence of significant mucocutaneous characteristics, palmar papules, panniculitis, interstitial lung disease (ILD), and clinically amyopathic dermatomyositis (CADM). When combined with rapidly progressing ILD (RP-ILD), anti-MDA5 DM can be fatal. The literature indicates that nervous system involvement is uncommon in patients with anti-MDA5 DM. We report a case of anti-MDA5 DM with neuropsychiatric abnormalities and ILD. The patient suffered from persistent worsening mental disorders, while his ILD was relatively stable. The patient's neuropsychiatric abnormalities gradually subsided after receiving treatment with glucocorticoids, immunoglobulins, and immunosuppressants, leaving only a slow response and memory loss.

B1-cell-produced anti-phosphatidylserine antibodies contribute to lupus nephritis development via TLR-mediated Syk activation.

Autoantibodies produced by B cells play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). However, both the cellular source of antiphospholipid antibodies and their contributions to the development of lupus nephritis (LN) remain largely unclear. Here, we report a pathogenic role of anti-phosphatidylserine (PS) autoantibodies in the development of LN. Elevated serum PS-specific IgG levels were measured in model mice and SLE patients, especially in those with LN. PS-specific IgG accumulation was found in the kidney biopsies of LN patients. Both transfer of SLE PS-specific IgG and PS immunization triggered lupus-like glomerular immune complex deposition in recipient mice. ELISPOT analysis identified B1a cells as the main cell type that secretes PS-specific IgG in both lupus model mice and patients. Adoptive transfer of PS-specific B1a cells accelerated the PS-specific autoimmune response and renal damage in recipient lupus model mice, whereas depletion of B1a cells attenuated lupus progression. In culture, PS-specific B1a cells were significantly expanded upon treatment with chromatin components, while blockade of TLR signal cascades by DNase I digestion and inhibitory ODN 2088 or R406 treatment profoundly abrogated chromatin-induced PS-specific IgG secretion by lupus B1a cells. Thus, our study has demonstrated that the anti-PS autoantibodies produced by B1 cells contribute to lupus nephritis development. Our findings that blockade of the TLR/Syk signaling cascade inhibits PS-specific B1-cell expansion provide new insights into lupus pathogenesis and may facilitate the development of novel therapeutic targets for the treatment of LN in SLE.

Olfactory ecto-mesenchymal stem cell-derived exosomes ameliorate murine Sjögren's syndrome by modulating the function of myeloid-derived suppressor cells.

Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by progressive inflammation and tissue damage in salivary glands and lacrimal glands. Our previous studies showed that myeloid-derived suppressor cells (MDSCs) exhibited impaired immunosuppressive function during disease progression in patients with SS and mice with experimental Sjögren's syndrome (ESS), but it remains unclear whether restoring the function of MDSCs can effectively ameliorate the development of ESS. In this study, we found that murine olfactory ecto-mesenchymal stem cell-derived exosomes (OE-MSC-Exos) significantly enhanced the suppressive function of MDSCs by upregulating arginase expression and increasing ROS and NO levels. Moreover, treatment with OE-MSC-Exos via intravenous injection markedly attenuated disease progression and restored MDSC function in ESS mice. Mechanistically, OE-MSC-Exo-secreted IL-6 activated the Jak2/Stat3 pathway in MDSCs. In addition, the abundant S100A4 in OE-MSC-Exos acted as a key factor in mediating the endogenous production of IL-6 by MDSCs via TLR4 signaling, indicating an autocrine pathway of MDSC functional modulation by IL-6. Taken together, our results demonstrated that OE-MSC-Exos possess therapeutic potential to attenuate ESS progression by enhancing the immunosuppressive function of MDSCs, possibly constituting a new strategy for the treatment of Sjögren's syndrome and other autoimmune diseases.

Relapsing granulomatosis with polyangiitis provoked by trauma: A case report.

RATIONALE: The precise cause of granulomatosis with polyangiitis (GPA) remains unclear. Herein we present a case of refractory GPA occurring after trauma. PATIENT CONCERNS: A 43-year-old man suffered fractures of the left orbital in an accident, and then received surgical repair. At a postoperative follow-up, he developed maxillary sinusitis. Seven months later, he was hospitalized with symptoms of cough, high-grade fever, and loss of weight. DIAGNOSIS: He was diagnosed with GPA based on the symptoms of upper and lower respiratory tract involvement, granulomas in a lung biopsy specimen, and presence of PR3-ANCA. INTERVENTIONS: Initially the patient responded well to the treatment of glucocorticoids and cyclophosphamide (CYC). Forty days later, he was hospitalized again with symptoms of fever, cephalgia, and recurrent ulcerated subcutaneous nodules, due to the vasculitic manifestations of GPA. This time he was treated with cyclophosphamide and glucocorticoids with no improvement, and then switched to rituximab. OUTCOMES: After 4 doses of rituximab, the symptom of cephalgia disappeared and subcutaneous ulcerations and conjunctival congestion diminished. LESSONS: Trauma may act as an inflammatory stimulus to affect the course of disease in GPA. The combination of glucocorticoids and cyclophosphamide is the standard therapy for GPA. Nevertheless, patients who have no response to CYC, especially with predominantly vasculitic manifestations, could resort to rituximab.