Investigation of Association of TYK2-P1104A Variant in Systemic Lupus Erythematosus Patients With or Without Tuberculosis

Systemic lupus erythematosus (SLE) is a complex disorder involving a hyperactive immune system. SLE is debilitating, with limited options for treatment. Recent advances in understanding the disease, its etiology, and genetics have made management more efficient. There has been a paradigm shift in the treatment over the past few decades from symptomatic management to the recent exciting reports of drug-free remission. Thus, detecting factors contributing to or protecting against the disease is paramount for better-personalized medicine. Additionally, infections due to SLE account for a majority of morbidity and mortality. Tuberculosis (TB) is one of the prevalent chronic infections that affect SLE patients, although the prevalence as well as mortality is high in countries in which TB is endemic. TYK2 (non-receptor tyrosine-protein kinase) is essential in generating immune responses by developing pro-inflammatory cytokines. P1104A mutation in TYK2 is a missense mutation and impairs the normal functioning of TYK2, in turn impairing the production/action of pro-inflammatory cytokines. TYK2-P1104A is beneficial in SLE patients and has a protective effect. However, due to impaired generation of cytokines and diminished response against TB, the possibility of TYK2-P1104A mutation in TB patients is high. The literature also points to the fact that the frequency of this allele is low in different populations, and the data related to its clinical effects is limited. Our study found no TYK2-P1104A allele in SLE patients, SLE patients who have TB, and TB patients, as well as healthy controls.