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.
Kimmel
Paul L
PL
Department of Medicine, Division of Renal Diseases and Hypertension, George Washington University Medical Center, 2150 Pennsylvania Avenue NW, Washington, DC 20037, USA. pkimmel@mfa.gwu.edu
Cohen
David J
DJ
Abraham
A Andrew
AA
Bodi
Istvan
I
Schwartz
Arnold M
AM
Phillips
Terry M
TM
D016263:AIDS-Associated Nephropathy / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D017471:Receptors, Interferon / Q000378:metabolism*; D014018:Tissue Distribution; D015854:Up-Regulation; D000096743:Interferon gamma Receptor
D018932:Chemokine CCL2; D018946:Chemokine CCL5; D000949:Histocompatibility Antigens Class II; D016898:Interferon-alpha; D016209:Interleukin-8; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor