Background/Purpose: Systemic lupus erythematosus (SLE) is a chronic, debilitating autoimmune disease characterized by heterogeneous, multiorgan involvement with female predominance. Lupus nephritis is one of the key complications of SLE with 10% of patients developing end-stage renal failure, and major risk for overall morbidity and mortality in SLE. The Klotho gene plays an important role in the process of aging, inflammation, and autoimmunity. Diminished levels of a-Klotho (Kl) were reported in age related diseases such as cancer, hypertension, and kidney disease. Significantly low a-Klotho levels were associated with an increased risk of progressive decline in renal function. The aim of our study was to evaluate the serum concentration of a-Klotho in patients with SLE only [Group I] ; SLE with hypertension (HTN)[Group II]; and SLE with lupus nephritis (LN) and HTN [Group III], and compare to that of healthy control and/or control with HTN to determine associations with disease and disease activity.

Methods: We used banked serum samples from patients and controls enrolled in a prospective longitudinal cohort study. Our study consisted of 20 paired serum samples from patients with SLE and/or LN and/or HTN (5 in each group) and 15 controls with or without HTN. SLE patients had serum collected during paired visits (first and second visit) with lower and higher disease activity determined through clinical and laboratory elements of the SLEDAI (SLE Disease Activity Index).The serum samples were analyzed through an enzyme-linked immunosorbent assay (ELISA) development system for the determination of human soluble a-Kl (R&D Systems).

Results: The serum concentration of Kl was 0.84 ± 0.599 ng/ml and 0.86 ± 0.449 ng/ml in SLE patients during inactive and active disease, respectively. Serum Kl averaged 0.82 ± 0.667 ng/ml in No HTN controls and 1.21 ± 1.252 ng/ml in HTN controls. Serum Kl negatively correlated with age among female SLE patients from all groups during active disease (r = – 0.524, p = 0.032). Interestingly, serum Kl concentration positively correlated with anti-dsDNA antibody levels in all females with active disease (r = 0.525, p = 0.046). Moreover, the serum Klotho concentration positively correlated with protein/creatinine ratio in females with active disease and LN (r = 0.974, p = 0.004). There was no association between Kl concentration and C3, C4 levels in SLE patients.

Conclusion: This is the first study measuring Kl levels in serum from the inactive and active stage of SLE with hypertension as a covariable. Klotho levels negatively correlated with age of SLE patients, which is similar to the diminished concentration of Kl seen with chronological aging. We initially postulated that Kl levels would decrease in SLE patients since serum Kl acts as an anti-inflammatory molecule, but did not see this in our study. Surprisingly, we found an association between Kl levels and the positivity of dsDNA titers and protein/creatinine ratio. The positive correlation between elevated levels of Kl and laboratory measures of disease activity may be a compensatory response to inflammation, while decreases with age may reflect accelerated immune senescence.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-%ce%b1-klotho-is-decreased-in-older-systemic-lupus-erythematosus-patients-and-correlate-with-markers-of-disease-activity/