Altered production of IgE and IgA induced by IL-4 in peripheral blood mononuclear cells from patients with IgA nephropathy

Abstract

SUMMARYIn order to elucidate the factors responsible for altered inimunoglobuHn production in patients with IgA nephropalhy (IgAN). the in vitro effeets of IL-4 and interferon-gamma (IFN-y) on the synthesis of IgH and IgA by peripheral blood mononuclcar cells (PBMC) were studied. Spontaneous IgE and IgA synthesis by PBMC was signifieantly increased in palienis with IgA nephropathy compared with eontrols. The maximum amounts of IgA and IgE synthesis by PBMC after stimulation with IL-4 were almost the same both in palients with IgAN and in eontrols. The enhaneemenl rale of IL-4-induced IgE and IgA synthesis was signihcanlly lower in IgAN than in the controls, suggesting in vivo preaetivation of PBMC in IgAN patients. IFN-7 suppressed IgA and IgE synthesis by PBMC from IgAN patients as well as controls. However, the suppressive effect on IgE synthesis was less prominent in patients with IgAN, These results suggested ihat altered IL-4 action might be involved in the development oflgA nephropathy. IgE [18]. In recent studies, increased expression of CD23 on peripheral blood lymphocytes has been reported in asthma [19]. atopic dermatitis [20). and in other atopie diseases [21.22] as well as in collagen diseases sueh as systemic lupus erythcmalosus (SLE) and rheumatic arthritis [23], Other reports showed elevated levels of lL-4 in sera from patients with Correspondence: Naohiro Yano, MI), Department oT Internal Medicine, Tokai University, Isehara, Kanagawa, 259-11, Japan, progressive systemic sclerosis [24], and expression of IL-4 mRNA in allergen-induced late-phase cutaneous reactions in atopie subjects [25], A study using I L-4-transgenie miee revealed thai IL-4 induces allcrgic-like inflammatory disease in systemic organs [26]. These studies strongly suggested that IL-4 plays some role in the development ofdiseases wiih allergie changes. The aim of ihe present study was to elueidate the role of IL-4 in altered production of IgE and IgA by peripheral blood mononuciear cells (PBMC) from patients with IgAN. Keywords MATERIALS AND METHODS PatientsTwenty-six patients with IgAN and 22 age-matched patients with non-IgA prolifcrative glomerulonephrilis (PGN) were selected randomly from patients who were diagnosed by open

Small RNA deep sequencing reveals novel miRNAs in peripheral blood mononuclear cells from patients with IgA nephropathy

“…The exact pathogenesis of IgAN is not well-defined, although it is characterized by the aberrant glycosylation and deposition of IgA in mesangial areas. Previous studies found that abnormal immune regulation is closely associated with the development of IgAN ( 3 , 9 , 12 , 13 ). Proliferating cell nuclear antigen expression increased in PBMCs, and the percentage of circulating B lymphocytes (CD19) increased in patients with IgAN ( 12 , 23 ), indicating abnormal proliferation of PBMC in the development of IgAN.…”

“…Peripheral blood mononuclear cells (PBMCs) are known to participate in IgA deposition and IgAN development, and previous studies have shown that miRNAs in PBMCs could promote the progression of IgAN ( 9 , 10 , 12 , 13 ). The miRNA expression profile of PBMCs in patients with IgAN has been studied by using a miRNA microarray, and miR-148b was found to be a potential promoter of IgAN ( 9 ).…”

Incidence and risk factors for recurrent Henoch-Schönlein purpura in children from a 16-year nationwide database

“…However, no study has addressed the correlation between recurrent HSP and allergic diseases. For instance, elevated serum Th2-related cytokine levels (such as interleukin [IL]-4 and IL-5, and IgE) were reported in children with HSP [ 31 – 34 ]. Most HSP occurred after bacterial or viral infections, insect bites, or even food allergies, suggesting that allergic reactions predispose to HSP initiation [ 26 , 35 ].…”

Expression of IgA class switching gene in tonsillar mononuclear cells in patients with IgA nephropathy

“…Several alterations related to IgA class switching in IgAN have been reported: namely, elevation of serum IgA [35,36], increases in circulating IgA immune complexes [37], increases in IgA-bearing cells in peripheral blood [38], and enhancement of in-vitro IgA production by peripheral blood mononuclear cells [39,40]. It is believed that there is a hyperproduction of IgA in IgAN, and potential mechanisms have been studied by many investigators [41,42]. Reports have been intriguing concerning the probable mechanisms of altered IgA production in IgAN.…”