Altered Fc galactosylation in IgG₄is a potential serum marker for chronic lung disease

Abstract

Characterising chronic lung diseases is challenging. New, less invasive diagnostics are needed to decipher disease pathologies and subphenotypes. Fc galactosylation is known to affect IgG function, and is altered in autoimmune disorders and under other pathological conditions. We tested how well Fc glycans in IgG from bronchoalveolar lavage fluid (BALF) and serum correlated, and if the Fc glycan profile could reveal pulmonary inflammation.A shotgun proteomics approach was used to profile Fc glycans in serum and BALF of controls (n=12) and sarcoidosis phenotypes (Löfgren's syndrome (LS), n=11; and non-LS, n=12). Results were further validated in severe asthma (SA) (n=20) and published rheumatoid arthritis (RA) patient data (n=13) including clinical information.Intra-individually, Fc-galactosylation status of IgG1 (R2=0.87) and IgG4 (R2=0.95) correlated well between matrixes. Following GlycoAge-index correction, the ratio between agalactosylated and digalactosylated Fc glycans of IgG4 could distinguish sarcoidosis and SA from healthy and RA subjects with a mean±se area under the curve (AUC) of 78±6%. The AUC increased to 83±6% using the more chronic lung disease types (non-LS and SA) and most strikingly, to 87±6% for the SA subgroup.The results indicate that the Fc galactosylation status of IgG4 is a potential blood test marker for chronic lung inflammation.

SpotLight Proteomics—A IgG-Enrichment Phenotype Profiling Approach with Clinical Implications

“…In this study, we could find several immune effector processing proteins that interact with the IgG-Fc region to be significantly elevated in the sarcoidosis patients (Figure 5). This trend was also in line with what was observed for the IgG-Fc-glycosylation pattern which was containing a significantly lower distribution of galactosylated forms [10]. We could also identify an elevation in the sarcoidosis patients in proteins involved in neutrophil activation/mediated immunity-, as well as cholesterol-, lipid-, and amyloid-regulating pathways (Figure 5).…”

“…However, importantly and as discussed above, most of the non-IgG detected features that were identified as sarcoidosis correlating have also been observed in previous studies [11,12,13,14,15]. Furthermore, the observed alteration in Fc-galactosylation status (which is known to be age dependent) remained significant following age correction [10].…”

Bilateral scrotal mass mimicking testicular cancer: An unusual presentation of sarcoidosis

“…Axitinib use in mRCC patients on hemodialysis has only been described in case reports. [6][7][8] Thus, to the best of our knowledge, this is the first case series on the efficacy and safety of axitinib in this population. The previous case reports also suggested the feasible efficacy and permittable safety of axitinib, consistent with the present findings.…”

“…The previous case reports also suggested the feasible efficacy and permittable safety of axitinib, consistent with the present findings. 6,7 In contrast, the impact of hemodialysis on the PK of axitinib remains controversial. 7,8 This discrepancy might be caused…”

“…A recent study showed that Fc glycosylation, known to affect IgG function, is altered in autoimmune disorders, and the Fc glycosylation status of IgG4 might serve as a biomarker for chronic lung inflammation. 6 Because sarcoidosis has a similar clinical phenotype to IgG4related diseases, we retrospectively compared the Fc glycosylation status of IgG4 among control participants (Ctrl, n = 5), patients with TC (n = 16), RF (n = 4) and the patient with sarcoidosis (the present patient, n = 1). We carried out analyses of lectin array assay of sera using GlcNAc-reactive lectin (F17AG), b-Gal-reactive lectin (CGL2) and biotin-anti-IgG4 Fc antibody (Fig.…”