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Vol. 19. Issue 4.
Pages 180-187 (April 2023)
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Vol. 19. Issue 4.
Pages 180-187 (April 2023)
Original article
Relative CTLA-4, PTPN-22, and interleukin 37 mRNA expressions in patients with lupus nephritis
Expresiones relativas de ARNm de CTLA-4, PTPN-22 e interleucina 37 en pacientes con nefritis lúpica
Nermeen Hassan A. Moneima, Marwa Mohamed Hosnyb,c, Hanan Hassan Omard,
Corresponding author
hananhassan1978@gmail.com

Corresponding author.
, Mai Mohamed Abdelnabya, Marwa Mohamed Fouade, Waleed Omar Abd El-Waheedf, Samah Hamdy Elmedanyg, Heba Mohamed Zakif
a Department of Physical Medicine, Rheumatology and Rehabilitation, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
b Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
c Oncology Diagnostic Unit Lab, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
d Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
e Department of Microbiology and Immunology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
f Department of Internal Medicine, Nephrology Unit, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
g Department of Physical Medicine, Rheumatology and Rehabilitation, Faculty of Medicine, Tanta University, Tanta, Egypt
Article information
Abstract
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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:
Systemic lupus erythematosus
CTLA-4
IL-37
PTPN-22
Lupus nephritis
Resumen
Objetivos

El lupus eritematoso sistémico (LES) es una enfermedad autoinmune caracterizada por la desregulación inmune de las células T, y la pérdida de tolerancia a los antígenos propios. CTLA-4 y PTPN-22 están involucrados en la inhibición de la activación de los linfocitos T. IL-37 es una citocina antiinflamatoria que suprime la inmunidad innata. La expresión relativa de CTLA-4, IL-37 y PTPN-22 se evaluó como reguladores negativos de la respuesta inmune en pacientes con LES, nefritis lúpica (NL) y actividad de la enfermedad.

Métodos

Se realizó PCR en tiempo real para determinar las expresiones relativas de ARNm de CTLA-4, IL-37 y PTPN-22 en 58 pacientes con LES, que se dividieron en 2 grupos: 29 pacientes con LES sin nefritis y 29 pacientes con NL frente a 50 controles.

Resultados

Hubo una expresión significativamente alta de los genes CTLA-4 e IL-37 en pacientes con LES en comparación con los controles (p=0,005; 0,018, respectivamente). No hubo diferencia en la expresión relativa del ARNm de PTPN-22 entre los pacientes con LES y los controles. La expresión relativa de ARNm de CTLA-4 disminuyó en pacientes con LN (p=0,044); sin embargo, la expresión relativa de ARNm de IL-37 se sobreexpresó en pacientes con LN (p=0,001) en comparación con aquellos sin LN. Hubo una sobreexpresión significativa de ARNm relativo de IL-37 y PTPN-22 en pacientes con LES activo. Pero hubo una diferencia no significativa en la expresión de CTLA-4 con la actividad de la enfermedad. El análisis de regresión reveló que los pacientes con sobreexpresión relativa de ARNm de IL-37 tenían el doble de riesgo de desarrollar nefritis lúpica (OR: 1,906; IC 95%: 1,218-2,983; p=0,005).

Conclusiones

La expresión relativa de ARNm de IL-37 fue elevada en pacientes con LES y se asoció con compromiso renal y actividad de la enfermedad. Podría considerarse como una nueva herramienta de predicción prometedora para LN. La expresión relativa del ARNm de PTPN-22 se correlacionó con la actividad de la enfermedad solo en pacientes con LES.

Palabras clave:
Lupus eritematoso sistémico
CTLA-4
IL-37
PTPN-22
Nefritis lúpica

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