IKZF1 polymorphisms are associated with susceptibility, cytokine levels, and clinical features in systemic lupus erythematosus

Abstract

Ikaros family zinc finger 1(IKZF1) encodes a lymphoid-restricted zinc finger transcription factor named Ikaros that regulates lymphocyte differentiation and proliferation as well as self-tolerance. Increasing evidence indicates that IKZF1 could contribute to the pathogenesis of autoimmune diseases. Recent research has provided evidence that IKZF1 might correlate with Systemic lupus erythematosus (SLE), but no clear definition has been made yet. In this study, we focus on the relationship between IKZF1 polymorphisms and SLE susceptibility, cytokine levels, and clinical characteristics in the Chinese Han population. One thousand seventy-six subjects, including 400 SLE patients and 676 healthy controls, were included in this study. Three single nucleotide polymorphisms within IKZF1 containing rs4917014, rs11980379, and rs4132601 were genotyped in all subjects by an improved multiplex ligation detection reaction technique. 143 subjects from SLE patients were randomly selected for testing the levels of serum cytokines. The clinical characteristics of SLE patients were gathered and collated from medical records. The data were analyzed mainly using SPSS20.0 (SPSS lnc., Chicago, IL). Significant relationships were observed between rs4132601 and SLE susceptibility, CD40 ligand, and malar rash ( P < .001, P = .04, and P = .01, respectively). In addition, significant relationships were observed between rs4917014 and susceptibility, granzyme B level, and hematological disorder in SLE ( P = .005, P = .03 and P = .005, respectively). The results further support that IKZF1 may have an important role in the development and pathogenesis of SLE. Allele G of rs4132601 and rs4917014 is related to a decreased risk of SLE occurrence and associated with clinical features in SLE patients, including CD40 ligand level, granzyme B level, malar rash, and hematological disorder, which play important roles in disease progression.

IKAROS in Acute Leukemia: A Positive Influencer or a Mean Hater?

“…These findings demonstrate that two opposing signal transduction pathways, the tumor suppressor PP1 pathway and the oncogenic CK2 pathway, converge on IKAROS and exercise their oncogenic or tumor suppressor effects by controlling its function [ 159 ]. Multiple malignancies, including leukemia, overexpress the multipotent serine/threonine kinase CK2 [ 160 ]. When CK2 is overexpressed in B-ALL, it inhibits IKAROS complex formation and attracts HDAC1 to the BCL2L1 promoter, which represses BCL2L1 and promotes BCL-XL expression [ 161 ].…”

Novel IKZF3 transcriptomic signature correlates with positive outcomes of skin cutaneous melanoma: A pan-cancer analysis

“…The disorder of its expression has the directive relationship with the hematological malignancies and primary immunodeficiency. Lack of Ikaros family may lead to a variety of immune related diseases, including immune thrombocytopenia ( Sriaroon et al, 2019 ), systemic lupus erythematosus ( Chen et al, 2020 ), rheumatoid arthritis ( Yang et al, 2019 ). For example, mutations of IKZF1–3 in leukemias are associated with poor prognosis, mainly caused by the disruption of lymphocyte fates ( Rebollo and Schmitt, 2003 ; Payne and Dovat, 2011 ).…”

The emerging role of noncoding RNAs in systemic lupus erythematosus: new insights into the master regulators of disease pathogenesis

“… 188 Numerous studies have shown an association between NEAT-1 and SLE. 189 Jiang et al evaluated the expression of NEAT1 in PBMC from patients with SLE and healthy individuals. NEAT1 was shown to be highly upregulated in the PBMC of SLE patients in this research.…”