Relative CTLA-4, PTPN-22, and interleukin 37 mRNA expressions in patients with lupus nephritis

Reumatol Clin (Engl Ed). 2023 Apr;19(4):180-187. doi: 10.1016/j.reumae.2023.03.004.

Abstract

Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by T-cell immune-dysregulation and loss of tolerance to self-antigens. CTLA-4 and PTPN-22 are involved in the inhibition of T-lymphocytes activation. IL-37 is an anti-inflammatory cytokine that suppresses innate immunity. The relative expression of CTLA-4, IL-37 and PTPN-22 were evaluated as negative regulators of immune response in SLE patients, lupus nephritis (LN) and disease activity.

Methods: Real-Time PCR was performed to determine relative CTLA-4, IL-37, and PTPN-22 mRNA expressions in fifty-eight SLE patients, who were divided into two groups: 29 SLE patients without nephritis and 29 patients with LN, versus fifty controls.

Results: There was a significantly high-expression of CTLA-4 and IL-37 genes in SLE patients compared to controls (p=0.005; 0.018 respectively). There was no difference in relative PTPN-22 mRNA expression between the SLE patients and controls. Relative CTLA-4 mRNA expression decreased in LN patients (p=0.044), however, relative IL-37 mRNA over-expressed in LN patients (p=0.001) compared to those without LN. There was a significant over-expression of relative IL-37 andPTPN-22 mRNA in active SLE patients. But, there was a non-significant difference in CTLA-4 expression with disease activity. Regression analysis revealed patients with relative IL-37 mRNA over-expression had two times more to develop lupus nephritis (OR=1.906, 95% CI=1.218-2.983, p=0.005).

Conclusions: Relative IL-37mRNA expression was elevated in SLE patients and associated with renal involvement and disease activity. It could be considered as a new promising predicting tool for LN. Relative PTPN-22 mRNA expression was correlated with disease activity only in SLE patients.

Keywords: CTLA-4; IL-37; Lupus eritematoso sistémico; Lupus nephritis; Nefritis lúpica; PTPN-22; Systemic lupus erythematosus.

MeSH terms

  • CTLA-4 Antigen / genetics
  • Humans
  • Interleukins
  • Lupus Erythematosus, Systemic* / genetics
  • Lupus Nephritis* / genetics
  • RNA, Messenger

Substances

  • CTLA-4 Antigen
  • Interleukins
  • RNA, Messenger
  • IL37 protein, human