Marker Of Sarcoidosis Research Articles

Delayed Cutaneous Hypersensitivity Tests and Lymphopenia as Activity Markers in Sarcoidosis

To evaluate new and already known biological markers of activity in patients with sarcoidosis. A 10-year prospective clinical evaluation, including a battery of delayed cutaneous hypersensitivity tests (DCHTs) and other markers of activity. Outpatient department of a university teaching hospital. Forty patients with biopsy-proven sarcoidosis were prospectively evaluated every 6 months. In this study, only the visits that fulfilled the situation of active period (AcP) or of asymptomatic period (AsP) were taken into account. Twenty-one visits were considered to be in the AcP, and 26 were considered to be in the AsP. Seven patients were studied both in the AcP and the AsP. DCHTs and blood sample extraction every 6 months. The mean diameter of the cutaneous wheal for each antigen (AG) was lower in the AcP group than in the AsP group (candidine, p < 0.0001; tuberculin, p < 0.0009; trichophytin, p < 0.02; streptokinase-streptodornase, p < 0.001). Also, the mean (+/- SD) diameter for the four AGs taken together was lower in the AcP group (2.3 +/- 4.2 mm) than in the AsP group (16.8 +/- 9.3 mm; p < 0.0001). The mean serum angiotensin-converting enzyme (S-ACE) value was higher in the AcP group than in the AsP group (p < 0.02). A low lymphocyte count and a percentage of the lymphocyte count (< 20%) also were detected more frequently in the AcP group than in the AsP group (p < 0.02 and p < 0.0001, respectively). DCHTs appear to be a simple, reliable, and easily performed marker of inflammatory activity in sarcoidosis patients. Furthermore, serum total and differential lymphocyte count and the S-ACE level proved to be useful inflammatory markers in this study.

Genotyping in the MHC locus: potential for defining predictive markers in sarcoidosis

In sarcoidosis, host genetic factors are discussed as contributing to disease susceptibility and course. Since tumor necrosis factor (TNF)-α is a central mediator of granuloma formation and since elevated TNF-α levels are found during active phases of sarcoidosis, genetic polymorphisms correlating with influences on TNF-α levels are of special interest. The complete sequencing of the MHC region and the increase in the number of identified gene polymorphisms in this locus associated with TNF-α production offer the opportunity of detecting new genes associated with sarcoidosis and perhaps of defining disease-associated haplotypes that bear the potential of serving as predictive markers for this disease.

Human leukocyte antigen-DRB1 position 11 residues are a common protective marker for sarcoidosis.

Genetic factors, in particular human leukocyte antigens (HLAs) are important determinants of susceptibility to sarcoidosis, a chronic granulomatous disease of undetermined etiology. To clarify the role of HLA in sarcoidosis we determined HLA-DR and -DQ alleles in case-control samples from three European populations (United Kingdom, Czech, and Polish) and compared these results with those published for three additional populations (Italian, Japanese, and Scandinavian) to determine whether the HLA-DR and/or -DQ alleles act as ethnic-dependent, or ethnic-independent modifiers of disease risk. Although variations were apparent in the alleles associated with susceptibility, reductions in the frequency of alleles associated with protection were remarkably consistent in the six populations. Previously detected associations between single-nucleotide polymorphisms at the TAP2 locus and sarcoidosis were shown to be due to linkage disequilibrium with the HLA-DR locus. The protective HLA-DR alleles, which encode the DR1 and DR4 antigens, were found to share characteristic small hydrophobic residues at position 11, which were replaced by small hydrophilic residues in the remaining, nonprotective, HLA-DR alleles. This residue position is within a pocket of the HLA-DR complex antigen binding groove (designated P6), where it is the only variable amino acid and therefore determines the peptide binding preferences of this pocket. A highly significant reduction in the frequency of individuals carrying HLA-DR alleles with a hydrophobic residue at position 11 was observed in the sarcoidosis cases in the three populations we examined. This suggests this HLA-DR residue is an important protective marker in sarcoidosis.

Elevated serum soluble CD44 level in sarcoidosis.

Sarcoidosis is a chronic multi-organ granulomatous disease of unknown etiology. Several studies have suggested an involvement of immunologic background in sarcoidosis. The lymphocyte surface marker CD44 is a multifunctional molecule which mediates the adhesion of lymphocytes to the extracellular matrix. Recently, we developed a system to quantitate soluble CD44 (sCD44) which we employed to determine serum and bronchoalveolar lavage fluid (BALF) levels of sCD44 to obtain further insights into immunologic aspects of sarcoidosis. Serum sCD44 levels were measured in 13 consecutive patients with sarcoidosis and 56 normal healthy controls using enzyme-linked immunoabsorbent assay. BALF sCD44 levels were also measured in 11 patients with sarcoidosis and 10 normal healthy controls. In patients with sarcoidosis, the serum sCD44 level was significantly higher than that of normal controls (348.5+/-164.2 ng/ml vs 145.4+/-22.9 ng/ml; p<0.001). Also BALF sCD44 levels tended to be higher in sarcoidosis than in normal controls (23.7+/-13.4 ng/ml vs 18.1+/-8.4 ng/ml), but no statistically significant difference was recognized. We also found that there was a positive correlation between the serum sCD44 and angiotensin converting enzyme (r=0.78). Our data indicate that sCD44 may be related to immunologic background and may be a useful new marker of sarcoidosis.

The angiotensin-converting enzyme DD gene is associated with poor prognosis in Finnish sarcoidosis patients.

Angiotensin-converting enzyme (ACE) genotypes may reflect prognosis in sarcoidosis. They were determined in 59 Finnish sarcoidosis patients and 70 healthy control subjects. The prognosis of the sarcoidosis patients was determined after follow-up for 1, 2, 3, 5 and >5 yrs and classified as good (normal chest radiograph and lung function, no signs of extrapulmonary disease activity within 2 yrs from diagnosis), intermediate (neither good nor poor) or poor (persisting unstable pulmonary infiltrates, vital capacity and diffusing capacity of the lung for carbon monoxide <50% predicted and/or extrapulmonary disease activity after >5 yrs follow-up). The DD, ID and II genotypes were found in 31 and 27%, in 54 and 49%, and in 15 and 24% of patients and control subjects respectively. The odds ratio (DD+ID to II) was 1.45 (95% confidence interval 0.60-3.49). The D alelle was found more often in patients (58%) and in control subjects (51%) than the I allele but the difference was not statistically significant. Statistically significantly more patients with the DD genotype had a poor prognosis compared with patients with II homozygotes and ID heterozygotes. Among 11 patients with Löfgren's syndrome (bilateral hilar lymphadenopathy and erythema nodosum), four had the DD genotype. Three of these patients had a prognosis despite presenting a clinical picture usually associated with a good prognosis. The angiotensin-converting enzyme genotype may be a prognostic marker in sarcoidosis and larger studies are warranted to define its clinical utility.

BIOCHEMICAL CHANGES IN SARCOIDOSIS

Biochemical markers in sarcoidosis are closely related to the immunological events and the activity of inflammatory effector cells at sites of granuloma formation. The markers can be measured in serum, then reflecting whole body concentration, or in BAL fluid, then indicating activity in the lung. Only calcium and ACE serum levels have gained a proven value in the clinical field.