Diagnostic Value of the CD103+CD4+/CD4+ Ratio to Differentiate Sarcoidosis from Other Causes of Lymphocytic Alveolitis

Abstract

Background: The CD103 integrin is present on CD4+ lymphocytes of the bronchial mucosa, but not on peripheral blood CD4+ lymphocytes. It has been hypothesized that CD4+ lymphocytes in pulmonary sarcoidosis originate from redistribution from the peripheral blood to the lung, and therefore do not bear the CD103 integrin. Some data suggest that a low CD103+ percentage among bronchoalveolar lavage fluid (BALF) CD4+ lymphocytes discriminates between sarcoidosis and other diagnoses. Objective: To determine the diagnostic value of BALF CD103+ to identify sarcoidosis among other causes of alveolar lymphocytosis in a large retrospective case series. Methods: Among 391 consecutive bronchoalveolar lavages performed at our institution and analyzed by flow cytometry, we identified 207 cases, which were grouped into nine diagnostic categories: sarcoidosis, tuberculosis, non-tuberculous infections, hypersensitivity pneumonitis, non-specific interstitial pneumonia, organizing pneumonia, drug-induced lung diseases, other interstitial lung diseases (ILDs), and other diagnoses. To assess the discriminative value of the CD103+CD4+/CD4+ ratio to distinguish sarcoidosis from other entities, areas under ROC curves (AUC) were calculated. Results: Sarcoidosis patients (n = 53) had significantly lower CD103+CD4+/CD4+ ratios than patients in other diagnostic categories. The AUC was 62% for sarcoidosis compared to all other diagnoses, and 69% for sarcoidosis compared to other ILDs. When combining CD103+CD4+/CD4+ and CD4+/CD8+ ratios, the AUC increased to 76 and 78%, respectively. When applying previously published cut-offs to our population, the AUC varied between 54 and 73%. Conclusions: The CD103+CD4+/CD4+ ratio does not accurately discriminate between sarcoidosis and other causes of lymphocytic alveolitis, neither alone nor in combination with the CD4+/CD8+ ratio, and is not a powerful marker for the diagnosis of sarcoidosis.

CD31+, CD38+, CD44+, and CD103+ lymphocytes in peripheral blood, bronchoalveolar lavage fluid and lung biopsy tissue in sarcoid patients and controls

“…Other authors (50)(51)(52)(53)(54)(55) have also revealed that BALF CD4 + T lymphocytes from sarcoidosis patients compared with other interstitial diseases have reduced CD103 expression.…”

“…However, Braun et al found no differences between the CD103 + and CD103populations with respect to pro-inflammatory parameters. (55).…”

Biomarkers in the Diagnosis and Prognosis of Sarcoidosis: Current Use and Future Prospects

“…The sensitivity and specificity seems to depend strongly on the population used in the study. Heron et al ( 84 ) and Bretagne et al ( 85 ) show a significant decrease in the CD103+CD4+/CD4+ ratio in sarcoidosis patients in comparison to other ILD while a study by Hyldgaard et al ( 79 ) does not show a similar decrease. The difference in outcome might be explained by the inclusion of patients without alveolar lymphocytosis by Hyldgaard et al ( 79 ).…”

Coexistent Sarcoidosis and Tuberculosis: A Case Report

“…Bronchoalveolar lavage does not accurately discriminate between sarcoidosis and other causes of lymphocytic alveolitis such as TB [11] . The case herein supports the hypothesis that systemic manifestation of sarcoidosis and its improvement with steroid treatment can occur coincidently with low-antigen, pleural TB.…”