Role and distribution of PENTRAXIN 3 (PTX3)in glomerular lesions of HIV positive patients

PTX3 is a prototypic member of the long pentraxin family. PTX3 is involved in innate resistance to pathogens, controlling inflammation and extracellular matrix remodelling. PTX3 binds to C1q and activates the complement cascade, stimulates fibroblasts, thus favouring collagen matrix deposition. PTX3 is produced in inflammatory conditions by different cells, such as fibroblasts, monocytes/macrophages, dendritic and endothelial cells. Glomerular involvement in HIV positive patients is characterized by a wide spectrum of lesions. The most peculiar glomerular lesion is HIV-associated nephropathy (HIVAN), which is characterized by focal and segmental glomerular sclerosis with prominent tuft collapse, hypertrophy /hyperplasia of podocytes, marked tubular/interstitial changes. Immune-complex glomerulonephritis (GN), such as membranoproliferative GN (MPGN), membranous GN (MGN), IgA nephropathy (IgAN), and other types of glomerular lesions not related to immune-complex deposition (i.e. non-collapsing focal segmental glomerusclerosis –NC-FSGS, minimal changes disease and other minor glomerulopathies) are also described in HIV population. Non-HIVAN glomerulopathies in seropositive patients are histologically similar to those observed in non HIV subjects, although some peculiar aspects are found. Immunological mechanisms, not completely clear so far, have been speculated to explain these particular differences. For this reason, glomerular disease in HIV patients could be an interesting field of research about the role of PTX3. The aim of the study was to assess PTX3 distribution in different types of HIV–related glomerular lesions, describing cell type production and correlation with histological lesions. Materials and methods. Thirty-one biopsies of cases with HIV glomerulopathies were tested for PTX3 expression by immunohistochemistry (IHC): 7 HIVAN, 2 MPGN, 4 MGN, 4 IgAN, 9 NC-FSGS, 4 end stage renal disease (ESRD). Twenty-two cases of glomerular diseases in HIV negative subjects, with comparable histological diagnosis, were selected as controls. Moreover, normal renal parenchyma was used to test PTX3 distribution in non inflamed renal tissue. IHC was performed on formalin-fixed paraffin embedded biopsies, by using affinity-purified rabbit IgG against human PTX3 (raised in our laboratory). Results. Normal renal tissue was negative for PTX3 expression. In HIV positive subjects, the higher PTX3 positivity was observed in cases of HIVAN, IgAN, MGN. NC-FSGS cases had a very low PTX3 expression. The positive staining was mainly in the interstitium; glomerular positivity was found in rare cases, with a mesangial pattern. The correlation between PTX3 positive areas and interstitial inflammatory infiltrate, sclerosis and C3c/C1q immunofluorescence deposition was lacking. Comparing PTX3 expression in HIV positive and negative subjects (even excluding HIVAN) was higher in HIV patients. Conclusions. These preliminary findings seem to support the role of HIV infection, and the following systemic immunomodulation, in the expression and distribution of the proinflammatory protein PTX3 in renal parenchyma of patients with glomerular disease.