Upregulation of MHC class II, interferon-alpha and interferon-gamma receptor protein expression in HIV-associated nephropathy.

BACKGROUND

Renal cellular HIV infection has been linked to the pathogenesis of HIV-associated nephropathy (HIVAN), but mediators of its development are unknown. HIV infection is associated with disordered cytokine metabolism, and chemokine receptors are coreceptors for HIV immune cellular infection. Chemokines such as interleukin (IL)-8, monocyte chemoattractant protein-1 (MCP-1) and RANTES, and interferons (IFNs) have been implicated in the progression of nephropathy. Renal major histocompatibility complex (MHC) protein expression is involved in antigen presentation and modulating tissue cellular immune responses. Their relative importance in HIVAN pathogenesis is unknown.

METHODS

We measured levels of chemokines, IFN-alpha, IFN-gamma receptor and non-polymorphic MHC Class II protein by high performance capillary electrophoresis, and incubation with antibodies for quantification by chemiluminesce in renal tissue of patients with HIVAN, compared with tissue without HIV infection, in the presence and absence of nephropathy. Renal biopsy tissue protein levels were correlated with the number and type of infiltrating tissue immune cells.

RESULTS

Mean renal interstitial and glomerular MCP-1, RANTES and IL-8 tissue levels were higher in patients with HIV infection compared with tissue without HIV infection, regardless of the presence of renal disease. In contrast, mean renal interstitial and glomerular non-polymorphic MHC Class II, IFN-alpha and IFN-gamma receptor protein were higher in patients with HIVAN compared with all other groups. Tissue MHC Class II and IFN-gamma receptor protein levels did not correlate with immune cellular infiltration in patients with HIV infection and renal disease.

CONCLUSIONS

The data suggest an upregulated renal immune microenvironment, capable of antigen presentation, exists in HIVAN. MHC Class II proteins and IFNs, and the capacity to present antigen may be crucial in HIVAN pathogenesis.