IgG Concentrations Distinguish People with Cystic Fibrosis and Mycobacterium abscessus

Excerpt

Respiratory infections with nontuberculous mycobacteria (NTM) are difficult to diagnose in people with cystic fibrosis (PwCF), as the CF lung is often colonized with numerous other bacteria and fungi that confound NTM detection [1]. In cases of suspected NTM infection in PwCF, an easily measured biomarker that correlates with the presence of NTM in the lung would benefit differential diagnosis. We recently reported [2] that high-frequency airway B cells distinguish PwCF and respiratory NTM infection (NTM^POS) from PwCF who are not infected with NTM (NTM^NEG). Since immunoglobulin (Ig) is a B-cell product that is routinely and easily measured in most clinical diagnostic laboratories, we performed a secondary analysis of the bronchoalveolar lavage fluid (BALF) samples collected for our previous study [2] to determine if airway levels of two immunoglobulin isotypes (IgG, IgM) corresponded to their NTM status. The results of this analysis are shown in Fig. 1 and demonstrate that BALF from NTM^POS PwCF had significantly higher concentrations of IgG relative to NTM^NEG PwCF (Fig. 1A, p < 0.0001). This pattern was also observed for IgM, albeit a less significant difference (Fig. 1B, p = 0.012). Only within our NTM^POS cohort were there several samples with IgG and IgM concentrations above the fit curve range of the assay (Meso Scale Diagnostics Isotyping Panel). The same data are expressed as individual and lobe-specific IgG and IgM values in Fig. 1C, D, respectively. As we reported, PwCF in our NTM^NEG and NTM^POS groups had concomitant, polymicrobial infections comprising S. aureus, P. aeruginosa, Aspergillus, and Candida spp. and were otherwise demographically similar; the only difference between both groups was the presence of NTM. Notably, BALF samples derived from individuals infected with M. abscessus (blue data points in Fig. 1A, B, NTM^NEG2-4 in Fig. 1C, D) were generally distinguished by higher IgG concentrations than those infected with M. intracellulare / M. chimaera (orange data points in Fig. 1A, B, NTM^NEG1 in Fig. 1C, D). Based on these results, we recommend the further examination of IgG in BALF (or other respiratory samples collected during standard-of-care) as it distinguishes CF-NTM^POS individuals in their patient communities. If broadly observed across multiple institutions, then we believe BALF IgG—an easily measured analyte—may benefit the differential diagnosis of NTM infection in PwCF.

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