Diagnosis of sarcoidosis.
ABSTRACT To describe the recent advances in the diagnostic procedures for sarcoidosis and explore future directions.
Novel imaging techniques have been explored in sarcoidosis, such as positron emission tomography using L-[3-F]-alpha-methyltyrosine, which is more specific for malignancy than F-fluorodeoxyglucose positron emission tomography. The combined modality of L-[3-F]-alpha-methyltyrosine-positron emission tomography with fluorodeoxyglucose-positron emission tomography could successfully discriminate sarcoidosis from malignancy. The finding of delayed enhancement in cardiac magnetic resonance imaging could identify cardiac involvement of sarcoidosis with higher sensitivity than echocardiography, thallium scintigraphy, and gallium scintigraphy. Endobronchial ultrasonograpy-guided transbronchial needle aspiration is a safe and useful tool for diagnosing sarcoidosis with a diagnostic accuracy, sensitivity and specificity of 85-93, 78-89, and 92-96%, respectively. Developments in genetics have demonstrated that 99% of the human leukocyte antigen DRB1*0301/DQB1*0201-positive patients with Löfgren's syndrome show a spontaneous remission, in contrast to only 55% of the human leukocyte antigen DRB1*0301/DQB1*0201-negative patients. These alleles could be novel promising factors for discriminating a prognosis in Löfgren's syndrome.
Recent development including novel imaging techniques, novel biopsy procedures, and genetic analyses could be of value for the diagnosis of sarcoidosis.
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ABSTRACT: Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of immune granulomas in involved organs. The cytokine profile in inflamed lesions of sarcoidosis is mainly determined by T helper 1 (Th1) cells. Interleukin 18 (IL-18) is primarily a monocyte/macrophage-derived cytokine. IL-18 has been recently identified as an IFNgamma-inducing factor. The cytokine plays an important role in the induction of Th1 response and it may be responsible for sarcoidosis progression. The aim of the study was to assess the usefulness of IL-18 estimation in the sarcoidosis diagnosis and the disease course prognosis. The diagnosis of sarcoidosis was established in 88 patients (the mean age of 38.1+/-10.8 years). We measured IL-18 level in plasma and bronchoalveolar lavage fluid (BALF) cell culture supernatant (CCS) using the enzyme-linked immunoassay technique (ELISA). We also performed the flow cytometric analysis of BALF lymphocyte phenotype. Statistica 5.0 and non-parametric tests: the Mann-Whitney U-test and the Spearman correlation test, were used for statistical analysis. The patient group consisted of 55 subjects without acute symptoms of sarcoidosis, 14 patients with acute Löfgren syndrome and 19 subjects with Löfgren syndrome in the past. Lung hilar lymphadenopathy was diagnosed in 49 patients and lung interstitial changes in 39 subjects. After 6-month-observation, 49 patients were in remission, 20 subjects manifested persistent disease and 19 patients had sarcoidosis progression. Plasma IL-18 level was significantly (P<0.0001) higher in sarcoidosis patients (383+/-250pg/ml) than in control subjects (146+/-72pg/ml). Plasma IL-18 level was similar both in subjects with Löfgren syndrome and in other patients. However, IL-18 level in BALF CCS was significantly (P<0.05) lower in Löfgren syndrome patients than in subjects without acute manifestation of the disease. The highest IL-18 level in plasma was found in patients with disease progression, in subjects with lung interstitial changes and in patients with extrapulmonary manifestation of the disease. We observed a positive correlation between plasma IL-18 level and the percentage of BALF lymphocytes (R=0.202, P=0.06) as well as the percentage of activated HLA DR+T cells (R=0.23, P<0.05). There was a negative correlation between the IL-18 level in BALF CCS and the percentage of BALF CD3-positive and CD4-positive lymphocytes (R=-0.27, -0.23, P<0.05). IL-18 may play a significant role in the prolongation of sarcoidosis course. Its estimation may become a good prognostic factor, which should be analyzed together with other factors useful in sarcoidosis monitoring.Respiratory Medicine 04/2007; 101(4):722-8. · 2.59 Impact Factor
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ABSTRACT: The BTNL2 gene is a member of the B7 receptor family that probably functions as a T-cell costimulatory molecule. It resides in the class II major histocompatibility complex (MHC) region of chromosome 6p and has recently been associated with sarcoidosis susceptibility in a white German population. We sought to replicate the BTNL2 association in an African American family-based study population (n=219 nuclear families) and two case-control populations--one African American (n=295 pairs) and one white (n=366 pairs). Ten SNPs were detected within a 490-bp region spanning exon/intron 5 of BTNL2. Haplotype variation within this region was significantly associated with sarcoidosis in all three study populations but more so in whites (P=.0006) than in the African American case-control (P=.02) or family-based (P=.03) samples. The previously reported BTNL2 SNP with the strongest sarcoidosis association, rs2076530, was also the SNP with the strongest association in our white population (P<.0001). The A allele of rs2076530 results in a premature exon-splice site and increases risk for sarcoidosis (odds ratio=2.03; 95% confidence interval 1.32-3.12). Although rs2076530 was not associated with sarcoidosis in either African American sample, a three-locus haplotype that included rs2076530 was associated with sarcoidosis across all three study samples. Multivariable logistic regression analyses showed that BTNL2 effects are independent of human leukocyte antigen class II genes in whites but may interact antagonistically in African Americans. Our results underscore the complexity of genetic risk for sarcoidosis emanating from the MHC region.The American Journal of Human Genetics 10/2005; 77(3):491-9. · 11.20 Impact Factor
- Internal Medicine - INTERNAL MED. 01/2007; 46(17):1387-1394.