Elevated 1, 25-dihydroxyvitamin D levels are associated with protracted treatment in sarcoidosis

Abstract

Summary Background Active vitamin D metabolite, 1, 25-dihydroxyvitamin D, has pleomorphic effects on both innate and acquired immunity. Sarcoid granuloma derived 1, 25-dihydroxyvitamin D leads to hypercalcemia, but the association of 1, 25-dihydroxyvitamin D with the clinical phenotype of the disease is currently unknown. Objective To determine the relationship between serum 1, 25-dihydroxyvitamin D levels and the degree of sarcoidosis disease chronicity. Design Serum 1, 25-dihydroxyvitamin D levels were measured and associated with sarcoidosis activity and phenotypes as assessed by Sarcoidosis Severity Score and Sarcoidosis Clinical Activity Classification respectively. Results Fifty nine patients were recruited with 44% having a sub-acute onset, and the chronic disease phenotype. There was no significant difference in serum 1, 25-dihydroxyvitamin D levels by chest radiograph stage (p = 0.092) nor did the levels correlate with the Sarcoidosis Severity Score (r = −0.16; p = 0.216). Serum 1, 25-dihydroxyvitamin D levels were associated with patients requiring repeated regimens of systemic immunosuppressive therapy or >1 year of therapy (SCAC Class 6). Increasing quartiles of serum 1, 25-dihydroxyvitamin D level was associated increased odds of the chronic phenotype (OR 1.82, 95% CI, 1.11, 2.99, p = 0.019). The majority (71%) of the patients with levels >51 pg/mL required chronic immunosuppressive therapy as defined by SCAC class 6. Conclusions In patients with sarcoidosis, elevated 1, 25-dihydroxyvitamin D levels are associated with chronic treatment needs.

Genome-wide association analysis reveals 12q13.3–q14.1 as new risk locus for sarcoidosis

“…This gene encodes a member of the cytochrome P450 superfamily. The enzyme activates vitamin D3, which has a well-established general immunoregulatory function [57,58] and also plays a role in lung immunity and in sarcoidosis [59,60]. Moreover, this gene has very recently been reported to be differentially expressed in sarcoidosis patients with a progressive-fibrotic, compared to a self-limiting, course of the disease [61].…”

Immunostimulation in the era of the metagenome

“…44 A cross-sectional analysis of 100 patients with autoimmune disease showed that a similar dynamic seems to occur in autoimmune disease. 45 Confirmation of this observation has been demonstrated in Crohn's disease 46 and rheumatoid arthritis, 44 with Kavathia et al tying higher levels of 1,25-D to greater disease severity in sarcoidosis patients, 47 and Mawer et al finding that 1,25-D levels were particularly elevated in the synovial fluid surrounding the joints of subjects with rheumatoid arthritis. 48 We have previously predicted, based on molecular in silico emulation, that at higher concentrations, 1,25-D interferes with expression of several of the body's other key nuclear receptors, including the glucocorticoid receptor, the androgen receptor and the thyroid receptor.…”

Difficulties of differential diagnostics of primary hyperparathyroidism and sarcoidosis of cervical lymph nodes

“…Предполагают, что 1,25(ОН) 2 D обладает иммунорегуляторными свой-ствами, подавляя, в частности, синтез IL-2 и γ-интерферона, участвующих в формировании сар-коидных гранулем и тем самым сдерживая некон-тролируемое гранулематозное воспаление [15]. Дру-гие авторы [16] считают, что внепочечная гиперпро-дукция 1,25(ОН) 2 D потенциируется цитокинами (в частности, γ-интерфероном) и повышенный уро-вень 1,25(ОН) 2 D отражает хроническое течение сар-коидоза. Описаны также случаи гиперкальциемии при саркоидозе на фоне нормального уровня 1,25(ОН) 2 D и повышенной концентрации PTHrP [3,10,17].…”