A. Warmold L. van den Wall Bake

Transforming growth factor-β inhibits the production of IgG, IgM, and IgA in human lymphocyte cultures

Abstract Transforming growth factor β (TGFβ) has potent immunoregulatory effects acting on both T and B cells. It strongly inhibits secretion of IgG and IgM in human and murine B cell cultures, but has been shown to have an enhancing effect on IgA production in the mouse. We have studied the effect of TGFβ on the production of IgA in human lymphocyte cultures. The addition of TGFβ to pokeweed-stimulated peripheral blood lymphocytes resulted in a suppression of IgA production of both subclasses, similar in magnitude to the suppression of IgG and IgM production. Membrane IgA expression was not increased by culturing tonsillar lymphocytes with TGFβ. In conclusion, we find no evidence for a selective enhancing effect of TGFβ on IgA synthesis in humans, in contrast to the findings reported in mice.

Cytokine-induced immunoglobulin production in primary IgA nephropathy.

Increased IgA synthesis probably plays a role in the pathogenesis of IgA nephropathy (IgAN). We investigated whether an increased sensitivity to the effect of various growth factor combinations leads to increased immunoglobulin synthesis by peripheral blood mononuclear cells (PBMC) from IgAN patients, in comparison to healthy controls. Although none of the growth factors studied (pokeweed mitogen [PWM], interleukin [IL]-2, IL-6, transforming growth factor-beta [TGF-beta], and combinations) led to greater IgA synthesis in IgAN patients than in controls, the IgA subclass ratio was shifted in favor of IgA1. In controls, but not in IgAN patients, IL-2 enhanced the production of IgA and IgA1 compared with media alone. This possibly reflects previous in vivo activation by IL-2 in IgAN patients. The suppressive effect of TGF-beta on immunoglobulin synthesis was modestly greater in IgAN patients than in controls. Increased production of IL-2 and perhaps other cytokines by T cells in vivo may be responsible for the elevated IgA immune response in these patients.

The Clinical Course of Minimal Change Nephrotic Syndrome With Onset in Adulthood or Late Adolescence: A Case Series

BACKGROUND Few studies have examined the treatment and outcome of adult-onset minimal change nephrotic syndrome (MCNS). We retrospectively studied 125 patients who had MCNS with onset in either adulthood or late adolescence. Presenting characteristics, duration of initial treatment and response to treatment, relapse patterns, complications, and long-term outcome were studied. STUDY DESIGN Case series. SETTING & PARTICIPANTS Patients with new-onset nephrotic syndrome 16 years or older and a histologic diagnosis of MCNS in 1985 to 2011 were identified from pathology records of 10 participating centers. OUTCOMES Partial and complete remission, treatment resistance, relapse, complications, renal survival. RESULTS Corticosteroids were given as initial treatment in 105 (84%) patients. After 16 weeks of corticosteroid treatment, 92 (88%) of these patients had reached remission. Median time to remission was 4 (IQR, 2-7) weeks. 7 (6%) patients initially received cyclophosphamide with or without corticosteroids, and all attained remission after a median of 4 (IQR, 3-11) weeks. 13 (10%) patients reached remission without immunosuppressive treatment. One or more relapses were observed in 57 (54%) patients who received initial corticosteroid treatment. Second-line cyclophosphamide resulted in stable remission in 57% of patients with relapsing MCNS. Acute kidney injury was observed in 50 (40%) patients. Recovery of kidney function occurred almost without exception. Arterial or venous thrombosis occurred in 11 (9%) patients. At the last follow-up, 113 (90%) patients were in remission and had preserved kidney function. 3 patients with steroid-resistant MCNS progressed to end-stage renal disease, which was associated with focal segmental glomerulosclerosis lesions on repeat biopsy. LIMITATIONS Retrospective design, variable treatment protocols. CONCLUSIONS The large majority of patients who had MCNS with onset in adulthood or late adolescence were treated with corticosteroids and reached remission, but many had relapses. Cyclophosphamide resulted in stable remission in many patients with relapses. Significant morbidity was observed due to acute kidney injury and other complications. Progression to end-stage renal disease occurred in a few patients and was explained by focal segmental glomerulosclerosis.

Intraperitoneal Administration of Tetanus Toxoid Elicits a Specific Response of Antibody-Secreting Cells in the Peritoneal Cavity

Anatomical studies suggested that the mammalian peritoneum plays an important role in immunological processes. Attention has primarily focussed on the greater omentum where “milky spots” cells play a role in the immunological defense of the peritoneal cavity.1,2,3,4,5 The peritoneal route of immunization has been used in experimental animals as an effective site for induction of both systemic and mucosal immune responses. 6,7,8 Kroese et al.9 showed that B cells from the murine peritoneal cavity repopulated the intestinal lamina propria of recipient mice with IgA-secreting cells. It was estimated that up to 50% of murine intestinal IgA-secreting cells were derived from surface IgA-negative precursor in the peritoneal cavity. Recently, Solvason et al.10 have demonstrated that human fetal omentum may serve as an additional site of B cell generation. These findings prompted us to study the potential of human peritoneal B cells to differentiate into antibody-secreting cells (AbSC). Patients on continuous ambulatory peritoneal dialysis (CAPD) represent a group of human subjects with a permanent access to the peritoneal cavity through an indwelling catheter.11 We immunized patients on CAPD intraperitoneally (i.p.) with tetanus toxid (TT), a well established protein antigen, to examine whether it can elicit specific antibody production by peritoneal B cells.