Reduced 25-OH vitamin D levels in patients with autoimmune citopenias: correlation with haematological parameters and clinical severity

Background: 25-OH vitamin D plays a crucial role in calcium and bone homeostasis, but it has also been shown to regulate several immune functions by acting on Th1/Th2 balance, T-reg activation and cytokine production. Vitamin D has been reported to be decreased in various autoimmune diseases such as multiple sclerosis and type 1 diabetes mellitus and to correlate with clinical outcomes. Aims: To evaluate 25-OH vitamin D values in patients with autoimmune cytopenias, namely primary immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA) and chronic idiopathic neutropenia (CIN), and to relate them with clinical severity and hematologic parameters. Methods: Clinical history, physical examination, complete blood count, serum samples and informed consent were collected at the time of enrolment, starting from January 2013. Hematologic parameters were also recorded at the time of the diagnosis. The number of immunosuppressive therapy lines (steroids, immunosuppressors, rituximab, splenectomy, and thrombopoietin agonists for ITP) and infectious episodes were retrospectively collected. Bleeding history was recorded for ITP. 25-OH vitamin D levels were evaluated in all patients and in 40 age and sex matched healthy controls, using an ELISA kit. Statistical analysis was performed using Student’t test for continuous variables and chisquare test for categorical variables. Results: Ninety-eight patients were enrolled, median age 59 years (range 17- 86), 32 males and 71 females. As regard hematologic parameters at enrollment, ITP patients (N=44) showed median platelets values of 73x103/mmc (7- 349x103/mmc) and vitamin D levels of 1.42 ng/mmc (0.21-8.69 ng/mmc), AIHA patients (N=35) displayed median Hb values of 11.6 g/dL (7.1-16.8 g/dL) and vitamin D levels of 1.94 ng/mL (0.09-6.71 ng/mL), and CIN cases (N=19) showed median ANCs values of 1.2x103/mmc (0.25-7x103/mmc) and vitamin D levels of 1.55 ng/mL (0.25-4.28ng/mL). As shown in figure 1, serum 25-OH vitamin D levels were significantly lower in patients than in controls (2.3±1.8 vs 6±6 ng/mL, mean values±SD, p<0.001), particularly in AIHA cases, regardless sex and age; considering the number of therapy lines vitamin D levels were reduced in AIHA patients who underwent two or more lines compared to cases with 0 or 1 line of therapy (1.7+1 ng/mL vs 2.8+1.8 ng/mL, p=0.04). As regards hematologic values at the time of diagnosis, all patients with vitamin D levels lower than 4 ng/mL showed significantly reduced Hb levels (9.3±3.5 vs 13.1±1.9 g/dL, mean values±SD, p<0.001) and absolute neutrophil counts (2.9±1.9 x103/mmc vs 4.3±2.1 x103/mmc, mean values±SD, p=0.001); the latter was particularly evident in CIN patients (0.57±0.3 x103/mmc vs 1.3±1.9 x103/mmc, mean values±SD, p<0.001). No relationship was found between hematologicparameters at diagnosis or at enrollment and vitamin D levels in patients with ITP. Considering infections, 15 grade 2 episodes occurred during the study time, of whom 6 in CIN patients, without relationship with hematologic parameters or with 25-OH vitamin D levels.Summary and Conclusion: This is the first demonstration of reduced values of vitamin D in autoimmune hematologic cytopenias. The reduction is particularly evident in AIHA cases with severe clinical picture and/or refractory to first line therapy and in CIN patients with more marked neutropenia. These data suggest a possible pathogenic role of reduced vitamin D in immune disregulation and provide hints for therapeutic options.