Background: Imbalance between pro and anti-inflammatory cytokines is an important feature in the pathogenesis of juvenile systemic lupus erythematosus (JSLE). Janus kinases (JAKs) play an important role in the regulation of action of these cytokines. Dysregulation of JAK pathway has been implicated in the pathogenesis of JSLE.
Objectives: Evaluate JAK3 expression in serum of JSLE patients with active disease in comparison to age-and gender-matched healthy controls, as well as JAK 3 expression in renal tissue in patients with biopsy proven Lupus nephritis (LN)
Methods: Forty-six children and adolescents with active JSLE were recruited from the Pediatric Rheumatology Unit at Assiut university Children hospital. The patients were evaluated clinically and SLE flare was measured using SLE disease activity index (SLEDAI). In addition to routine and immunological laboratory work up, serum JAK3 expression was measured using polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Renal JAK 3 expression was done for 26 patients with clinical and laboratory features of LN where renal biopsy was done.
Results: The mean (SD) age of the studied patients was 12.2 (2.4) years, they were 34 females (74%) and 12 males (26%). Serum JAK3 expression both by ELISA and PCR were significantly higher among pateints as compared to the control group (p<0.000). Also, serum and renal JAK 3 expression both by PCR and ELISA were significantly positively correlated with anti-double stranded DNA and SLEDAI and significantly negatively correlated with serum complement 3 (p <0.000) Renal JAK 3 expression was significantly positively correlated with 24 hours urinary proteins and urinary RBCs (p<0.000) Both serum and renal JAK 3 expression were comparable between patients with proliferative LN and those with non-proliferative LN.
Conclusion: JAK 3 seems to have a major role in the pathogenesis of JSLE and strongly related with SLE flare and therefore use of JAK-3inhibitors could represent a targeted therapy of juvenile SLE.
Correlation between JAK 3 expression in serum and markers of activity of JSLE
Serum JAK 3 expression | C3 | C4 | Anti-dsDNA | ALC | SLEDAI score | |
---|---|---|---|---|---|---|
PCR | r-value | -0.677 | -0.692 | 0.818 | -0.221 | 0.842 |
P -value | 0.000* | 0.000* | 0.000* | 0.140 | 0.000* | |
ELISA | r-value | -0.622 | -0.679 | 0.823 | -0.354 | 0.887 |
P -value | 0.000* | 0.000* | 0.000* | 0.016* | 0.000* |
JAK: kanus kinase; C: complement; anti-dsDNA: anti double stranded DNA; ALC: absolute lymphocytic count; SLEDAI score: systemic lupus erythematous disease activity index
Correlation between JAK 3 expression in renal tissue and markers of activity of JSLE
Renal JAK 3 expression | C3 | C4 | Anti-ds DNA | SLEDAI score | |
---|---|---|---|---|---|
PCR | r-value | -0.931 | -0.693 | 0.787 | 0.822 |
P -value | 0.000* | 0.001* | 0.000* | 0.000* | |
ELISA | r-value | -0.842 | -0.858 | 0.822 | 0.868 |
P -value | 0.000* | 0.000* | 0.000* | 0.000* |
JAK: kanus kinase; C: complement; anti-dsDNA: anti double stranded DNA; SLEDAI score: systemic lupus erythematous disease activity index
REFERENCES: NIL.
Acknowledgements: NIL.
Disclosure of Interests: None declared.