IgA nephropathy (IgAN) is the most common type of glomerular nephritis worldwide. For a long time it has been considered rather benign, but between 30 and 50 % of the patients will eventually develop dialysis-dependent chronic kidney disease [
1]. Some patients with morphological signs of IgAN also have IgA vasculitis (IgAV, formerly named Henoch Schönlein purpura) [
2,
3]. Patients with IgAN have galactose-deficient IgA (gd-IgA) in their circulation. The gd-IgA easily forms large immune-complexes, which are deposited in the mesangium [
4]. These deposits are a key feature of the disease, together with mesangial proliferation and an expanded mesangial matrix, and are used for histopathological diagnosis of IgAN [
5]. Several growth factors and cytokines have been suggested to be involved in the proliferation and expansion of the mesangial matrix, most notably PDGF and TGFβ1 [
6]. Investigation of PDGFB gene expression in IgAN has shown that there is an increase of PDGFB in patients with IgAN [
7], and stimulation of mesangial cells in vitro with PDGF increases their expression of several cytokines and growth factors such as IL-6 and TGFβ1 [
8]. IL-6 is a cytokine known to increase in mesangial cells when stimulated with gd-IgA. It has been suggested to be a prognostic marker for IgAN, but its role is still debated [
9,
10] Data showing that the complement system (alternative and lectin-pathways) are of importance in IgAN are also accumulating [
11]. However, the molecular mechanisms behind the highly variable onset and progression of these glomerular diseases are still elusive. There are familial forms of IgAN [
12,
13] where gd-IgA is found in the circulation of asymptomatic relatives. A Finnish investigation of kidneys from suicide or trauma victims revealed that 6.8 % of the kidneys contained IgA depositions although they had no other signs of disease. In a Japanese study of healthy kidney donors, 16.1 % of the investigated kidneys contained IgA deposits [
14,
15]. However it is not known if these deposits contain gd-IgA. Indeed, 60 % of transplanted patients diagnosed with IgAN develop deposits in their kidney graft. [
16‐
19] However, the clinical disease recurs in less than half (22–33 %) of the transplanted patients [
20‐
22]. Based on these facts, we wanted to investigate the role of the mesangial cells in development of IgAN. Since there is no specific way to evoke IgAN in cell culture and existing animal models are debated we developed a technique to culture mesangial cells from glomeruli retrieved directly from patient biopsies. Cells were either stimulated with purified IgA1 from IgAN patients (gd-IgA) or with IgA1 from healthy subjects (cIgA). Gene expression levels of cytokines, growth factors and matrix molecules and release of cytokines and growth factors into the cell medium were investigated as well as the proliferative response to PDGF. We were able to demonstrate that mesangial cells from patients with IgAN are significantly more reactive to IgA1 and PDGF stimulation and the cells express and produce higher levels of certain growth factors, cytokines and matrix components.