Israel Medical Association Journal

Background: Vitamin D insufficiency is associated with autoimmune and chronic inflammatory diseases such as tuberculosis and sarcoidosis. 

Objectives: To evaluate the vitamin D-dependent mechanisms of immunity and autoimmunity in different forms of pulmonary tuberculosis and sarcoidosis.

Methods: We measured the serum levels of 25(OH)D and 1,25(OH)2D, individual autoimmune profiles, plasma concentrations of cathelicidin, several hormones, and production of nine cytokines in patients with short- and long-duration tuberculosis and sarcoidosis.

Results: The level of 25(OH)D was significantly decreased in all patients. Concentration of 1,25(OH)2D was elevated only in sarcoidosis, prolactin content was augmented only in tuberculosis. We saw no expected increase of cathelicidin levels in tuberculosis and sarcoidosis. The individual mean immune reactivity levels of autoantibodies to 24 antigens were significantly lower in tuberculosis and sarcoidosis patients compared to healthy controls. Pronounced deviations from individual mean immune reactivity levels were found for several autoantigens in all patients. The induced production of interferon gamma-γ, interleukin (IL) 2, 17, and 8 by peripheral blood mononuclear cells was significantly increased in patients of both tuberculosis groups, but spontaneous production of tumor necrosis factor-α, IL-2, and IL-6 was lower in the tuberculosis patients than in healthy controls. We registered marked differences in the groups of tuberculosis patients. 

Conclusions: We demonstrated the role of vitamin D deficiency in poor cathelicidin response in  tuberculosis and sarcoidosis. Both diseases are accompanied by significant changes in the autoimmune profile, probably related to the status of vitamin D and cytokine regulation. 

 

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease with multiorgan involvement and wide variability in presentation and course. Although it can appear at any age, women of childbearing age are primarily affected. This has led to the proposal of a hormonal role in the development of SLE. Among the main hormones shown to have immunomodulatory effects are estradiol, progesterone and prolactin.

Objectives: To report the levels of estradiol and prolactin in SLE patients and establish the relationship between these levels and disease activity, and to determine whether the phases of the menstrual cycle influence the activity of SLE and its relationship to hormone levels.

Methods: In this cross-sectional study, we examined 60 women with SLE. We measured disease activity using SLEDAI and BILAG. We obtained peripheral blood samples to determine the levels of estradiol, progesterone, and prolactin. 

Results: Patients’ age ranged between 16 and 65 years and the mean disease duration was 5.5 years (0–20). SLE was active (SLEDAI > 6) in 13 patients and inactive in 47. Thirty patients were in a pre-ovulatory menstrual cycle phase, 13 in a post-ovulatory cycle, and 17 were menopausal. We found a significant association between C4 levels and disease activity (P = 0.01) and between estradiol levels and disease activity in the kidney (P = 0.04). We did not find hyperprolactinemia in any patient. 

Conclusions: In this population, we found an association between estradiol levels and organ-specific activity in the kidney. One may speculate as to whether our population might benefit from the implementation of anti-estrogen therapy for control of disease activity, particularly in the kidney.

 

Background: Multiple sclerosis (MS) is a common demyelinating disorder of the central nervous system (CNS) and although it is a well-established autoimmune disease its ethiopathogenesis has yet to be fully elucidated. The disease may present in several clinical forms that are closely associated with disease morbidity. In recent years various environmental and hormonal factors have been implicated in the pathogenesis of autoimmunity.

Objectives: To evaluate ferritin and prolactin levels in MS patients and their correlation with clinical manifestations of the disease.

Methods: Serum samples from 150 multiple sclerosis patients were evaluated for demographic characteristics, clinical parameters as well as prolactin and ferritin levels utilizing the Liaison chemiluminescent immunoassays (DiaSorin, Italy). Sera from 100 matched healthy donors were used as controls.

Results: Hyperprolactinemia was documented in 10 of 150 MS patients (6.7%) and hyperferritinemia in 12 (8%), both of which were significantly more common in this group compared with healthy controls (P ≤ 0.01 and P = 0.02 respectively). Among female MS patients, elevated prolactin levels were related to the secondary progressive type of disease (P = 0.05), whereas hyperferritinemia was associated with male gender (P = 0.03) and with the relapsing progressive type of the disease (P = 0.02). An inverse association was found between hyperferritinemia and the relapsing-remitting type of MS in male patients (P = 0.05)

Conclusions: Our results suggest a plausible association between these biomarkers and certain clinical types and gender among MS patients. Further studies combining clinical data, CNS imaging and these markers are warranted.
 

Background: Previous studies have suggested that prolactin may serve as an indicator of disease progression in breast cancer.

Objectives: To evaluate the use of PRL as a serum tumor marker in patients with breast cancer.

Methods: PRL serum level was determined in 99 breast cancer patients and compared with CA 15-3 serum level.

Results: Elevated serum level of PRL (>20 ng/ml) was found in 8 of 99 patients (8.1%). A stratified analysis of prolactin levels according to therapy revealed that PRL levels was increased in 8 of 55 untreated patients (14.5%), but not in patients who received hormonal or chemotherapy in the 3 months preceding the test (0/42 patients, P=0.009). However, mean PRL level was similar in patients with no evidence of disease activity and in patients with active disease (10.2 vs. 8.2 ng/ml, NS). In comparison, CA 15-3 mean level was significantly lower in patients with no evidence of disease as compared to patients with active disease (18.2 vs. 144.7 units/ml, P<0.001). PRL level was increased in 6 of 60 patients (10%) with no evidence of disease and in 2 of 39 (5.2%) with active disease (NS). In comparison, CA 15-3 level was increased in 3 of 60 patients (5%) with no evidence of disease and in 24 of 39 (61.5%) with active disease (P<0.001).

Conclusions: PRL levels are decreased following hormonal or chemotherapy in patients with breast cancer and there is no correlation between PRL serum level and the state of disease. Further studies are needed to clarify a possible clinical significance of hyperprolactinemia in a subset of patients with breast cancer.

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PRL = prolactin