Studying IFN-gamma, IL-17 and FOXP3 in pediatric lupus nephritis.

Abstract

BACKGROUND:

We studied the cytokines secreted by the inflammatory T cell subgroups (IFN-γ and IL-17) and FOXP3 expression in lupus nephritis (LN) and analyzed associations with clinical and histopathological parameters.

METHODS:

Renal tissue samples of 39 LN patients were studied. Immunohistochemical staining was carried out with antibodies against IFN-γ, IL-17, and FOXP3.

RESULTS:

Both IFN-γ (+) and IL-17+ cells were statistically higher in LN tissues when compared with controls (p < 0.01). The cells in the tubulointerstitium were CD3 + CD4+ displaying a Th1 and Th17 phenotype, whereas the less intense population in the glomeruli was CD3-CD4-. Interstitial CD3 + CD4+ FOXP3+ cells were also significantly higher in LN biopsies than in control tissues (p < 0.01). IFN-γ (+) and IL-17+ cells were more intense among class IV LN as compared to class II, III LN (p < 0.01 and p = 0.001, respectively). Subsequently, when IL-17 and IFN-γ staining was compared between the proliferative LN classes, class III and IV patients had more intense staining compared to class II (all p < 0.05). IFN-γ immunostaining correlated positively with serum creatinine and negatively with albumin levels and glomerular filtration rate (GFR). IL-17 immunostaining correlated with proteinuria, requirement for pulse steroids, and SLEDAI renal score, and negatively with GFR. Furthermore, glomerular and interstitial IL-17 and IFN-γ stainings were significantly associated with various parameters of histological activity (p < 0.05).

CONCLUSION:

We suggest that IFN-gamma and IL-17 could have a role in the pathogenesis and progression of LN. The Th1 and Th17 cells may be imperative in the severity of LN. Recognizing the complexity of the immune pathways involved in lupus reminds us that targeting B cells only may not suffice to control the progression of the inflammation.

• Authors: Mutlu Uysal Yazici, Diclehan Orhan, Gulsev Kale, Nesrin Besbas, Seza Ozen
• Journal: Pediatric nephrology (Berlin, Germany) (Pediatr Nephrol) Vol. 29 Issue 5 Pg. 853-62 (May 2014) ISSN: 1432-198X [Electronic] Germany
• PMID: 24482023 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FOXP3 protein, human
• Forkhead Transcription Factors
• Interleukin-17
• Interferon-gamma

Topics

• Adolescent
• Age of Onset
• Biopsy
• Child
• Female
• Forkhead Transcription Factors (biosynthesis, genetics, metabolism)
• Humans
• Immunohistochemistry
• Interferon-gamma (biosynthesis, genetics, metabolism)
• Interleukin-17 (biosynthesis, genetics, metabolism)
• Lupus Nephritis (genetics, metabolism, pathology)
• Male