Disease relevance of Sarcoidosis

• Hypercalcemia in an anephric patient with sarcoidosis: evidence for extrarenal generation of 1,25-dihydroxyvitamin D [1].
• Expression of the Fc receptor for IgE (Fc epsilon R) was analyzed on alveolar macrophages (AM) in 10 patients with extrinsic allergic alveolitis (EAA) compared with 10 patients with sarcoidosis and to 6 apparently healthy controls [2].
• In the context of the known compartmentalization of spontaneous IL 2 production and T cell proliferation at sites of disease in active pulmonary sarcoidosis, these IL 2R positive blood T cells would probably have a proliferative advantage if they trafficked to sites of active sarcoidosis, such as the lower respiratory tract [3].
• In this article, Graham Rook and John Stanford propose that a group of idiopathic diseases that are often associated with a degree of autoimmunity and arthritis, including rheumatoid arthritis, inflammatory bowel disease, sarcoidosis and psoriasis, are caused by extremely slow-growing bacteria [4].
• Diabetes mellitus must be considered when an assay of serum angiotensin-converting enzyme is used to confirm a diagnosis of sarcoidosis [5].

Psychiatry related information on Sarcoidosis

• AIM: To assess lung involvement and the association of demographic and psychosocial factors with respiratory health in 736 persons with sarcoidosis at enrollment in A Case Control Etiologic Study of Sarcoidosis (ACCESS) [6].

High impact information on Sarcoidosis

• Sarcoidosis is associated with a truncating splice site mutation in BTNL2 [7].
• Impaired counterregulation of glucose in a patient with hypothalamic sarcoidosis [8].
• The effects of chloroquine on serum 1,25-dihydroxyvitamin D and calcium metabolism in sarcoidosis [9].
• We studied the efficacy of chloroquine in two patients with sarcoidosis who were unable to tolerate the dosage of corticosteroids required to control hypercalciuria and prevent the formation of renal stones [9].
• However, lung cells from 9 of 10 patients with sarcoidosis and high-intensity alveolitis spontaneously released interleukin-2, and in a proportion that correlated with the proportion of T cells in the lung washings (P less than 0.01) [10].

Chemical compound and disease context of Sarcoidosis

• Letter: Levamisole in sarcoidosis [11].
• Sarcoidosis was diagnosed, and prednisone was administered [12].
• Characterization of 1 alpha-hydroxylation of vitamin D3 sterols by cultured alveolar macrophages from patients with sarcoidosis [13].
• We also examined the tissue factor and Factor VII activities of freshly lavaged alveolar cells from nine subjects with clinical and/or histologic evidence of sarcoidosis [14].
• Serum angiotensin-converting enzyme in sarcoidosis and other diseases [15].

Biological context of Sarcoidosis

• Here, we carried out a systematic three-stage SNP scan of 16.4 Mb on chromosome 6p21 in as many as 947 independent cases of familial and sporadic sarcoidosis and found that a 15-kb segment of the gene butyrophilin-like 2 (BTNL2) was associated with the disease [7].
• These studies confirm a genetic predisposition for sarcoidosis and present evidence for the allelic variation at the HLA-DRB1 locus as a major contributor [16].
• Eight single-nucleotide polymorphisms in CCR2 were studied in a total of 304 Dutch individuals (90 non-Löfgren sarcoidosis, 47 Löfgren's syndrome, 167 control subjects) [17].
• Typing two additional markers in this region revealed that DQCAR-G51152 haplotypes, spanning a 38-kilobase region across the HLA-DQB1 gene, were associated with sarcoidosis on a global level (p = 0.022) [18].
• In patients with sarcoidosis, the majority of pulmonary T lymphocytes were CD4+ cells that expressed low levels of CD27 antigen and an upregulation of CD95 and CD70 molecules [19].

Anatomical context of Sarcoidosis

• Consistent with this observation, lung lymphocytes from patients with active sarcoidosis, a disease in which lung lymphocytes are spontaneously releasing IL-2, did express NK cell activity (P less than 0.01) [20].
• Mean activity of angiotensin converting enzyme was elevated generally more than 10-fold in granuloma-containing lymph nodes, but not in lung in which normally it is abundant, in 19 of 20 patients with sarcoidosis [21].
• CD1d was found to be expressed in hepatocytes in all cases examined, and in epithelioid granuloma cells in 19 of 22 PBC livers and in 4 of 4 livers with hepatic sarcoidosis [22].
• Hypercalcemia in human granuloma-forming diseases like sarcoidosis results from the endogenous overproduction of 1,25-dihydroxyvitamin D [1,25-(OH)2D] by disease-activated tissue macrophages [23].
• Cyclosporine therapy of central nervous system sarcoidosis [24].

Gene context of Sarcoidosis

• The HLA-DPB1 locus also contributed to susceptibility for sarcoidosis and, in contrast to chronic beryllium disease, a non-E(69)-containing allele, HLA-DPB1*0101, conveyed most of the risk [16].
• In contrast, the analysis of the cytokine profile in sarcoidosis patients revealed a Th1 cell cytokine pattern characterized by increased concentrations of IL-2 and IFN-gamma but normal levels of IL-4 or IL-5 [25].
• The level of VEGF was evaluated by enzyme-liked immunosorbent assay in bronchoalveolar lavage fluid (BALF) from normal smokers, nonsmoking volunteers, idiopathic pulmonary fibrosis, pulmonary fibrosis associated with a connective tissue disease, and sarcoidosis [26].
• IP-10, however, was particularly increased in subjects with sarcoidosis (P <.001) [27].
• Sarcoidosis patients had higher frequencies of cells positive for IFN-gamma, IL-4, and IL-2 in their blood than did healthy controls, a finding that may reflect the systemic nature of sarcoidosis [28].

Analytical, diagnostic and therapeutic context of Sarcoidosis

• Angiotensin converting enzyme in lymph nodes from subjects with sarcoidosis was similar to the enzyme from normal lung and lymph node with respect to activity as a function of pH, inhibition of activity by EDTA and o-phenanthroline, gel filtration on Sephadex G-200, and requirement for chloride for activity, but appeared to be more heat labile [21].
• Patients were assessed for the following signs of sarcoidosis: typical changes on chest radiography or computed tomography; predominantly CD4 lymphocytosis in bronchoalveolar lavage fluid; elevated serum angiotensin-converting enzyme levels; elevated gallium uptake; and noncaseating granuloma on biopsy [29].
• Another patient had positive sputum cultures for Histoplasma capsulatum 5 years after initial diagnosis of sarcoidosis, but showed no improvement in the pulmonary infiltrate after treatment with amphotericin B [30].
• Because of hepatic involvement owing to sarcoidosis, results of serial liver function tests were not useful in determining which patients would have this reaction to methotrexate [31].
• Using PCR with sequence-specific primers, IL-1alpha -889, IL-1beta -511, IL-1beta +3953, and IL-1Ra intron 2 VNTR polymorphisms were determined in 348 white subjects of West Slavonic ancestry (95 patients with sarcoidosis, 54 patients with IPF, and 199 healthy control subjects) [32].

References