Lupusnephritis.

Lupus nephritis represents the most common visceral organ manifestation of systemic lupus erythematosus and has a major impact on lupus related morbidity and quality of life. Histologically, renal lupus involvement exhibits a broad range of patterns, which cause diverse clinical manifestations, ranging from mild asymptomatic urinary test abnormalities to severe nephrotic syndrome or rapidly progressive renal failure. Therapeutic options have considerably improved over the last decades, but despite intensive research efforts continue to be based on relatively unspecific immunosuppression. Given their considerable side effects, immunosuppressive treatments must be well tailored to the severity of lupus nephritis. For such a rational treatment planning, the exact histological diagnosis based on kidney biopsy plays a central role. This review article summarizes the basis of pathogenesis, histological manifestations, clinical pictures, diagnosis and treatment approaches of lupus nephritis.

Potential aggregation-prone regions in complementarity-determining regions of antibodies and their contribution towards antigen recognition: a computational analysis.

PURPOSE: To analyze contribution of short aggregation-prone regions (APRs), which may self-associate via cross-beta motif and were earlier identified in therapeutic mAbs, towards antigen recognition via structural analyses of antibody-antigen complexes. METHODS: A dataset of 29 publically available high-resolution crystal structures of Fab-antigen complexes was collected. Contribution of APRs towards the surface areas of the Fabs buried by the cognate antigens was computed. Propensities of amino acids to occur in APRs and to be involved in antigen binding were compared. Coincidence between APRs and individual CDR loops was examined. RESULTS: All Fabs in the dataset contain at least one APR in CDR loops and adjacent framework beta-strands. The average contribution of APRs towards buried surface area of Fabs is 16.0 +/- 10.7%. Aggregation and antigen recognition may be coupled via aromatic residues (Tyr, Trp), which occur with high propensities in both APRs and antigen binding sites. APRs are infrequent in the heavy chain CDR 3 (H3) loops (7%), but are frequent in H2 loops (45%). CONCLUSIONS: Co-incidence of APRs with antigen recognition sites can potentially lead to the loss of function upon aggregation. Rational structure-based design or selection strategies are suggested for biotherapeutics with improved druggability while maintaining potency.

Types of immune complexes in the ascitic fluid of women with carcinoma of the ovary.

Immune complexes with C1q-fixing properties and those precipitable by polyethylene glycol (PEG) were detected in ascitic fluid from patients with advanced ovarian cancer. The ascitic fluid from 42 of 58 patients (72%) contained these complexes. A positive result with the C1q assay was obtained in 41% of patients, whilst with the PEG assay a positive result was obtained in 59% (50% in the IgM, 36% in the IgG, and 14% in the IgA fraction). The highest mean level of PEG-precipitable complexes was in the IgG fraction (11.4 mg/100 ml) and lowest in the IgA fraction (3.3 mg/100 ml). These results indicate that gram quantities of the immune complexes may be isolated from the large volumes of ascitic fluid usually present in ovarian cancer. Further studies of ascitic fluid may thus provide data on the nature of the immune responses in these patients.