Human Immunoglobulin A

Introduction: Obsessive-Compulsive Disorder (OCD) is a disabling mental condition that its proteomic profiling is not yet investigated. Proteomics is a valuable tool to discover biomarker approaches. It can be helpful to detect protein expression changes in complex disorders such as OCD. Methods: Here, by the application of 2D gel electrophoresis (2DE), a pilot study of serum proteome profile of females with washing subtype of OCD was performed. Serum samples were obtained from females with washing subtype of OCD. Following the protein extraction from the serum with acetone perception, the samples were subjected to 2DE for separation based on pI and molecular weight (MW) with triple replications. Finally, the protein spots were visualized using Coomassie blue staining method and analyzed by Progenesis SameSpots software. Furthermore, protein-protein interaction (PPI) network analysis was handled by the application of Cytoscape software. Results: The results suggested that 41 matched spots demonstrated significant expression alterations among which 5 proteins including immunoglobulin heavy constant alpha-1 (IGHA1), apolipoprotein A-4 (APOA4), haptoglobin (HP), protein alpha-1-antitrypsin (SERPINA1), and component 3 (C3) were identified by database query. Additionally, PPI network analysis indicated the central role of SERPINA1 and C3 in the network integrity. However, albumin (ALB), amyloid precursor protein (APP), and protein alpha-1-antitrypsin (APOA1)proteins were important in OCD PPI network as well. The identified proteins were related to 3 processes: acute-phase response, hydrogen peroxide catabolic process, and regulation of triglyceride metabolic process. Conclusion: It was concluded that these proteins may have a fundamental role in OCD pathogenesis. Moreover, the dysregulation of inflammatory and antioxidant systems in OCD risk was suggested by the current study. However, evaluation of bigger sample sizes and application of mass spectrometry are essential requirements to confirm this preliminary evaluation.

Immunoglobulin class-switch recombination (CSR) and somatic hypermutations (SHMs) are prerequisites for antibody and immunoglobulin receptor maturation and adaptive immune diversity. The mismatch repair (MMR) machinery, consisting of homologs of MutS alpha, MutL alpha, and MutS beta (MSH2/MSH6, MLH1/PMS2, and MSH2/MSH3, respectively) and other proteins, is involved in CSR, primarily acting as a backup for nonhomologous end-joining repair of activation-induced cytidine deaminase-induced DNA mismatches and, furthermore, in addition to error-prone polymerases, in the repair of SHM-induced DNA breaks. A varying degree of antibody formation defect, from IgA or selective IgG subclass deficiency to common variable immunodeficiency and hyper-IgM syndrome, has been detected in a small number of patients with constitutional mismatch repair deficiency (CMMRD) due to biallelic loss-of-function mutations in one of the MMR genes (PMS2, MSH6, MLH1, or MSH2). To elucidate the clinical relevance of a presumed primary immunodeficiency (PID) in CMMRD, we systematically collected clinical history and laboratory data of a cohort of 15 consecutive, unrelated patients (10 not previously reported) with homozygous/compound heterozygous mutations in PMS2 (n = 8), MSH6 (n = 5), and MLH1 (n = 2), most of whom manifested with typical malignancies during childhood. Detailed descriptions of their genotypes, phenotypes, and family histories are provided. Importantly, none of the patients showed any clinical warning signs of PID (infections, immune dysregulation, inflammation, failure to thrive, etc.). Furthermore, we could not detect uniform or specific patterns of laboratory abnormalities. The concentration of IgM was increased in 3 out of 12, reduced in 3 out of 12, and normal in 6 out of 12 patients, while concentrations of IgG and IgG subclasses, except IgG4, and of IgA, and specific antibody formation were normal in most. Class-switched B memory cells were reduced in 5 out of 12 patients, and in 9 out of 12 also the CD38(hi)IgM(-)plasmablasts were reduced. Furthermore, results of next generation sequencing-based analyses of antigen-selected B-cell receptor rearrangements showed a significantly reduced frequency of SHM and an increased number of rearranged immunoglobulin heavy chain (IGH) transcripts that use IGHG3, IGHG1, and IGHA1 subclasses. T cell subsets and receptor repertoires were unaffected. Together, neither clinical nor routine immunological laboratory parameters were consistently suggestive of PID in these CMMRD patients, but previously shown abnormalities in SHM and rearranged heavy chain transcripts were confirmed.