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PubMed · 7575057

Altitude-dependent decrease in plasma fibronectin.

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C Wenisch, B Parschalk, S Reichmann, W Graninger, C Gruber. 1995-10-09. Altitude-dependent decrease in plasma fibronectin.. https://pubmed.ncbi.nlm.nih.gov/7575057/

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Acute-Phase Proteins↗

N-linked glycosylations at Asn(26) and Asn(114) of human MD-2 are required for toll-like receptor 4-mediated activation of NF-kappaB by lipopolysaccharide.

MD-2 is physically associated with Toll-like receptor 4 (TLR4) and is required for TLR4-mediated LPS signaling. Western blotting analysis revealed the presence of three forms of human (h)MD-2 with different electrophoretic mobilities. After N-glycosidase treatment of the cellular extract prepared from cells expressing hMD-2, only a single form with the fastest mobility was detected. Mutation of either one of two potential glycosylation sites (Asn(26) and Asn(114)) of MD-2 resulted in the disappearance of the slowest mobility form, and only the fastest form was detected in hMD-2 carrying mutations at both Asn(26) and Asn(114). Although these mutants were expressed on the cell surface and maintained its ability to associate with human TLR4, these mutations or tunicamycin treatment substantially impaired the ability of MD-2 to complement TLR4-mediated activation of NF-kappaB by LPS. LPS binding to cells expressing CD14, TLR4, and MD-2 was unaffected by these mutations. These observations demonstrate that hMD-2 undergoes N-linked glycosylation at Asn(26) and Asn(114), and that these glycosylations are crucial for TLR4-mediated signal transduction of LPS.

Acute-Phase Proteins↗

["Catastrophic systemic lupus erythematosus" with Rosai-Dorfman sinus histiocytosis. Successful treatment with anti-CD20/rutuximab].

HISTORY AND ADMISSION FINDINGS: A 59-year old woman was admitted with a four-month history of polyarthritis, myalgias and photosensitivity insufficiently responsive to methotrexate, corticosteroids and azathioprin. On physical examination she presented with symmetric ankle edema, polyserositis, petechial bleeding and swelling of cervical, axillary and inguinal lymph nodes. INVESTIGATIONS: Laboratory analysis revealed a trilinear cytopenia without signs of hemolysis. Acute phase proteins were elevated. Furthermore antinuclear antibodies, anti-phospholipid IgM antibodies, hypocomplementemia, a spurious IgGkappa paraprotein were noted. CT scans confirmed lymphadenopathy and revealed a pleural and pericardial effusion. Bone marrow biopsy showed marked hypercellularity and polyclonal plasmocytosis. Based on these findings systemic lupus erythematosus was initially suspected. However when abdominal MRI showed a retroperitoneal mass, an extensive histological workup, which also included lymph nodes and spleen, revealed numerous plasma cells and histiocytes in dilated sinuses, diagnostic of Rosai-Dorfman sinus histiocytosis. TREATMENT AND COURSE: High dose corticosteroids, intravenous gamma-globulin and repeated courses of cyclophosphamide failed to improve the pancytopenia, as did splenectomy. The patient was given the anti-CD20 monoclonal antibody Rituximab and all signs and symptoms improved dramatically. 18 months after the last treatment, the patient is in complete clinical and hematological remission. CONCLUSIONS: Sinus histiocytosis of Rosai/Dorfman can be associated with or mimic severe SLE. Rituximab, an anti-CD20 monoclonal antibody, may improve the antibody-mediated pathogenetic mechanism underlying both entities.

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