CLINICAL IMMUNO1,0(;1 .XND IMMUI\‘OI’A’1’HOI,Oi;~ Vol. 63, No. 2, May, pp. 19G199, 1992 The Role of lnterleukin 2 (IL-2) and Serum-Soluble Cells in Idiopathic IgA Nephropathy M. PARERA,* F. RIVERA,? J. EGIDO,$ AND A. CAMPOS? IL-2 Receptor *Hospital de Elda (SVS), iHospital de Alicante LSVS), and §Centro de ‘Transfusih, Departamento de Medicina, Unwersidad de Alicanfe. and #Funo!ucih Jimhez D&z, Facultad de Medicina, Uniuersidad Autdnoma, Madrid. Spain Interleukin 2 (IL-2) plays a central role in the immune response and may be involved in the derangement of cellular immunoregulation of idiopathic IgA nephropathy (IpAN). The aim of this study was to investigate the serum levels and production of IL-2 from peripheral blood mononuclear cells (PBMC) and the distribution of IL-2 receptor cells and se- rum-soluble IL-2 receptor cells (sIL-2R) in patients with IgAN. Twenty-four patients with IgA nephropathy and 11 healthy controls (age and sex matched) were studied during an infection-free period without signs of clinical activity at the moment of the study. Serum IL-2 concentrations did not differ between patients and controls. The supernatant levels of IL-2 taken from 24-hr cultures of PBMC stimulated with phytohemagglutinin or tumor necrosis factor increased sig- nificantly in the patients but not in the controls. The per- centage of IL-2R positive cells (CD25+) was increased in patients compared with controls. Moreover, IgAN patients had increased activated CD4+ lymphocytes when compared with the controls. Serum levels of sIL-2R were significantly higher in patients than in controls. There were no correla- tions among renal function, serum IgA levels, and urinary findings with cellular subsets or with IL-2 levels. However, sIL-2R was higher in the subgroup of patients with episodic macrohematuria and was closely related with the presence of red blood ceils in the urinary sediment. We conclude that PBMC of IgA nephropathy patients have an overproduction of IL-2 after mitogenic stimulation, an increased helper T cell activity, increased IL-2R+ cells, and elevated serum lev- els of sIL-2R. These alterations are present in periods of apparent clinical inactivity. Finally, sIL-2R is closely re- lated with hematuria, providing a good marker for disease activity. Our results suggesta pivotal role of IL-2 in cellular immune responses with regard to T cell activation in pa- tients with IgAN. 0 1992 Academic Press. Inc. INTRODUCTION Idiopathic IgA nephropathy (IgAN) has a wide vari- ety of clinical and pathological features with a predom- inance of mesa&al IgA deposition (1). The granular pattern of these deposits and the presence of circulat- ing immunocomplexes support the role of an altered humoral immune response to still unknown foreign an- tigens (2). Moreover, several authors have found dis- turbances associated with the cellular arm of the im- mune response: high levels of T lymphocytes with sur- face receptors for the Fc portion of IgA (3) that could promote IgA-specific B cell hyperactivity (4-7) and an abnormal imbalance between helper and suppressor/ cytotoxic T lymphocytes (4,5,8-13). Interleukin 2 (IL- 2) is a polypeptide produced by activated T cells that plays a pivotal role in the proliferation of T effector lymphocytes after antigenic stimulation. Upon activa- tion the T cell expresses high-affinity receptors for IL-2 (IL-2R) (14). Subsequently, a soluble form of the IL-2R protein (sIL-2R) is released to the medium. Indeed, the release of sIL-2R appears to be a characteristic marker of T lymphocyte activation and seemingly plays a reg- ulatory function during normal and abnormal cell growth and differentiation (15-17). Thus, it seems that IL-2 might participate in the pathogenesis of IgAN. There are only a few studies on this subject, but the results obtained have shown an overproduction of IL-2 both spontaneously 118) or upon mitogenic stimulation (19). The aim of this study was to investigate further the role of IL-2 and its relationship to lymphocyte subsets and to clinical and analytical data. MATERIAL AND METHODS Patients and Controls We studied 24 patients (18 males, 6 females) with biopsy-proven mesangial IgAN without clinical or bio- logical evidences for hepatic or systemic diseases. The ages were 33.6 * 2.8 years. Eleven patients had bouts of recurrent macrohematuria and 13 had asymptomat- ic urinary abnormalities or hypertension. The time elapsed from the diagnosis to the study was 58.1 rt 10.8 months. The mean serum creatinine was 1.8 + 0.3 mg/ dl. Normal renal function (serum creatinine cl.5 mg/ dl or CCr > 80 ml/m) was present in 13 cases; 8 pa- tients had moderate chronic renal failure (serum cre- atinine between 1.5 and 3 mg/dl) and 3 had serum creatinine >3 mg/dl but none were in dialysis treat- 196 0090-1229/92 $1.50 Copyright 0 1992 by Academic Press, Inc. All rights of reproduction in any form reserved.