Antibodies Research Articles

Immune Globulin Subcutaneous 16.5% in Treatment of Primary Immunodeficiency: A Two-Year, Multi-Center Analysis

Immune Globulin Subcutaneous 16.5% in Treatment of Primary Immunodeficiency: A Two-Year, Multi-Center Analysis

A Detailed Protocol for Constructing a Human Single-Chain Variable Fragment (scFv) Library and Downstream Screening via Phage Display.

The development of monoclonal antibodies (mAbs) represents a significant milestone in both basic research and clinical applications due to their target specificity and versatility in therapeutic and diagnostic applications. The innovative strategy of mAb screening, utilizing phage display, facilitates the in vitro screening of antibodies with high affinity to target antigens. The single-chain variable fragment (scFv) is a subset of mAb derivatives, known for its high binding affinity and smaller size-just one-third of that of human IgG. This report outlines a detailed and comprehensive procedure for constructing a scFv phagemid library derived from human patients, followed by screening via phage display affinity selection. The protocol utilizes 348 primer combinations spanning the entire human antibody repertoire to minimize sequence bias and maintain library diversity during polymerase chain reaction (PCR) for scFv generation, resulting in a library size greater than 1 × 108. Furthermore, we describe a high-throughput phage display screening protocol using enzyme-linked immunosorbent assay (ELISA) to evaluate more than 1200 scFv candidates. The generation of a highly diverse scFv library, coupled with the implementation of a phage display screening methodology, is expected to provide a valuable resource for researchers in pursuit of scFvs with high affinity for target antigens, thus advancing both research and clinical endeavors.

Multi-omic characterization of acquired resistance to immune checkpoint inhibitors in patients with metastatic renal cell carcinoma.

459 Background: While immune checkpoint inhibitors (ICI) have improved outcomes in patients (pts) with metastatic renal cell carcinoma (mRCC), acquired resistance (ARX) is commonly encountered. We aimed to characterize the genomic and transcriptomic correlates underlying ARX in ICI-treated mRCC patients. Methods: We identified pts with mRCC at Dana-Farber Cancer Institute and Fox Chase Cancer Center, treated with ICI-based regimens who had an initial response to therapy followed by disease progression. Tissue samples from the primary tumors or metastases were collected before ICI treatment and after ARX from a treatment-emergent escape lesion. Whole exome sequencing (WES) and bulk RNA-sequencing (RNA-seq) were performed. Somatic mutations were called using the Cancer Genome Analysis pipeline. Differential gene expression analysis (DGE) was run using DESeq2, followed by gene set enrichment analysis (GSEA). Immune cell fractions were estimated using CIBERSORTx. Cell fraction and tertiary lymphoid structures (TLS) scores were compared between post and pre-ARX samples using the Wilcoxon test. Results: A total of 41 samples (n=23 pre-ARX and n=18 post-ARX) were collected from 14 unique patients. After quality control, WES and RNA-seq data were available for 27 samples (14 pre-ARX and 13 post-ARX) and 9 samples (3 pre-ARX and 6 post-ARX), respectively. No discernable enrichment of gene mutations was detected in the post-ARX setting compared to the pre-ARX. DGE identified 61 downregulated immunoglobulin genes in the post-ARX setting. GSEA revealed significant depletion of pathways associated with B-cell and T-cell function in post-ARX samples (all adjusted p<0.05). Similarly, a trend towards decreased naïve B cell and CD8+ T cell fractions was observed in the post-ARX setting (p=0.17 for both). Three previously reported TLS-associated expression signatures were depleted in the post-ARX samples compared to pre-ARX (p=0.015, p=0.065 and p=0.065, respectively). Immunohistochemistry assessment of 3 samples from one pt using ant-CD3 and CD20 antibodies confirmed the presence of TLS in the pre-ARX sample and their absence in two different post-ARX samples. Conclusions: In our cohort of pts with mRCC, no gene mutations were implicated as drivers of ARX. However, ARX was associated with downregulation of B-cell signaling and humoral mediated immunity, as well as absence of TLS. Ongoing efforts are in progress to include more samples.

Tissue-Matched IgH Gene Rearrangement of Circulating Tumor DNA Shows Significant Value in Predicting the Progression of Diffuse Large B Cell Lymphoma.

Evidence has demonstrated that monitoring of the variable, diversity, and joining gene segments (VDJ) rearrangement of the immunoglobulin (Ig) genes in the circulating tumor DNA (ctDNA) is of value in predicting the outcomes of diffuse large B cell lymphoma (DLBCL). In this study, we investigated the role of VDJ rearrangement proportion in ctDNA for predicting DLBCL progression. Patients diagnosed with newly diagnosed DLBCL were included in this study. The VDJ sequences of IgH were detected using next-generation sequencing (NGS) in formalin-fixed paraffin-embedded tissue and/or peripheral blood. The clonotype of the highest proportion in the peripheral blood was defined as the "dominant circulating clonotype," whilst the clonotype of the highest proportion in matched tissue that is detected in peripheral blood was defined as the "dominant tissue-matched clonotype." The decision tree, a machine learning-based methodology, was used to establish a progression-predicting model through a combination of "dominant tissue-matched clonotype" proportion or "dominant circulating clonotype" proportion, and the clinicopathological information, including age, sex, cell of origin, stage, international prognostic index, lactate dehydrogenase, number of extranodal involvements and β2-microglobulin. A total of 55 patients with eligible sequencing data were used for prognosis analysis, among which 36 patients had matched tissue samples. The concordance rate of "dominant circulating clonotype" and "dominant tissue-matched clonotype" was 19.44% (7/36). The decision tree model showed that the combination of extranodal involvement event and "dominant circulating clonotype" proportion (≥37%) had a clinical value in predicting the prognosis of DLBCL following combined chemotherapy (sensitivity, 0.63; specificity, 0.81; positive prediction value (PPV), 0.59; negative prediction value, 0.83; kappa value, 0.42). Noticeably, the combination of the "dominant tissue-matched clonotype" and extranodal involvement event showed a higher value in predicting the progression (sensitivity, 0.85; specificity, 0.78; PPV, 0.69; kappa value, 0.64). IgH proportion detected in the ctDNA samples traced from tissue samples has a high clinical value in predicting the progression of DLBCL.

New peptides against B16F10 interfere in cell cycle of melanoma cells

Peptides have fantastic functions; they can act interfering in various cellular mechanisms such as the cell cycle. Furthermore, because of their high specificity, peptides can be used in antitumor therapy against specific targets. In this work we describe the in vitro action of four antitumor peptide against B16F10 melanoma cells, obtained from immunoglobulin genes. As a result, we show that peptides interfered in the cell cycle of B16F10 cells. In conclusion the present article describes a molecule from immunoglobulin with future potential for in vivo therapeutic test.

Humoral profiles of toddlers and young children following SARS-CoV-2 mRNA vaccination

Although young children generally experience mild symptoms following infection with SARS-CoV-2, severe acute and long-term complications can occur. SARS-CoV-2 mRNA vaccines elicit robust immunoglobulin profiles in children ages 5 years and older, and in adults, corresponding with substantial protection against hospitalizations and severe disease. Whether similar immune responses and humoral protection can be observed in vaccinated infants and young children, who have a developing and vulnerable immune system, remains poorly understood. To study the impact of mRNA vaccination on the humoral immunity of infant, we use a system serology approach to comprehensively profile antibody responses in a cohort of children ages 6 months to 5 years who were vaccinated with the mRNA-1273 COVID-19 vaccine (25 μg). Responses are compared with vaccinated adults (100 μg), in addition to naturally infected toddlers and young children. Despite their lower vaccine dose, vaccinated toddlers elicit a functional antibody response as strong as adults, with higher antibody-dependent phagocytosis compared to adults, without report of side effects. Moreover, mRNA vaccination is associated with a higher IgG3-dependent humoral profile against SARS-CoV-2 compared to natural infection, supporting that mRNA vaccination is effective at eliciting a robust antibody response in toddlers and young children.

DOP27 Systemic antibody responses against gut microbiota flagellins implicate shared and divergent immune reactivity in Crohn's Disease and chronic fatigue syndrome

Abstract Background Patients with Crohn’s disease (CD) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) exhibit elevated antibody responses against gut microbiota flagellins. However, flagellin-specific antibody repertoires and functional roles in the diseases remain incompletely understood. Bacterial flagellins can be categorized into three types depending on their interaction with toll-like receptor 5 (TLR5): (1) "stimulator" and (2) "silent" flagellins, binding TLR5 through a conserved N-terminal motif, with only stimulators activating TLR5 due to a specific C-terminal domain; (3) "evader" flagellins of pathogens, which circumvent TLR5 activation via mutated N-terminal TLR5 binding motifs. Here we studied the characteristics, epitope binding, and sequence (dis)similarity of anti-flagellin antibody responses in CD and ME/CFS. Methods Since conventional antibody profiling methods like enzyme-linked immunosorbent assays [ELISAs] do not allow for large-scale measurements of antibody repertoires, we leveraged phage-display immunoprecipitation sequencing (PhIP-Seq) to characterize 344,000 rationally selected peptide antigens in 256 patients with CD, 40 patients with ME/CFS and in two equally sized groups of age- and sex-matched healthy controls from population-based cohorts in the Netherlands and U.K., respectively. Different sequence alignment strategies were employed to compare flagellin peptide structures with observed antibody-bound flagellin peptide reactivity. Results Both patients with CD and ME/CFS exhibited elevated antibody responses against distinct regions of flagellin peptides compared to healthy individuals (P<0.001). N-terminal binding to Lachnospiraceae flagellins was comparable in both diseases, while C-terminal binding was more prevalent in CD. N-terminal antibody-bound flagellin sequences were similar across CD and ME/CFS, resembling ‘stimulator’ and ‘silent’ flagellins more than evaders. However, C-terminal antibody-bound flagellins showed higher resemblance to stimulator than to silent flagellins in CD, but not in ME/CFS. This group of antibody-bound flagellins was exclusively identified in a subset (10-20%) of patients with CD and characterized by its strong overrepresentation (exceeding 20-fold), underscoring its potential significance in distinguishing pathophysiologic subtypes of CD. Conclusion Antibody binding to the N-terminal domain of stimulator and silent flagellins may impact TLR5 activation in both CD and ME/CFS patients. Furthermore, elevated antibody binding to the C-terminal domain of stimulator flagellins in CD may explain pathophysiological differences between diseases. Our results highlight the diagnostic potential of these antibody responses and their impact on innate/adaptive immunity balance.

DOP20 Changes in systemic antibody epitope repertoires from preclinical to established Inflammatory Bowel Disease

Abstract Background Inflammatory bowel diseases (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), exhibit unique immunological changes early in development. Although >300 IBD-specific antibody responses have been identified1, systemic antibody epitope repertoires of preclinical IBD remain elusive. This study aimed to profile systemic antibody responses at unprecedented depth in individuals before and after the onset of IBD, aiming to identify preclinical disease biomarkers. Methods This study included individuals participating in the Lifelines Cohort Study, a large prospective population-based cohort study in the Netherlands including 167,000 individuals with longitudinal follow-up. Participants without IBD at baseline were screened for any reported IBD diagnosis during follow-up (2006-2021). Individuals who reported IBD during follow-up and with available serum samples were included. Samples at baseline (pre-diagnosis) and during follow-up (post-diagnosis) were used to profile antibody repertoires against 344,000 rationally selected microbial-, food-, and immune antigens using phage-display immunoprecipitation sequencing (PhIP-Seq). Results A total of 178 individuals with new-onset IBD were identified (Fig. 1). Median follow-up time until diagnosis was 3.9 (IQR: 3.4-4.3) years. Most individuals reported newly developed UC (n=123, 69.1%), followed by CD (n=44, 24.7%), and undetermined IBD (IBD-U, n=11, 6.2%). A total of 5,174 antibody responses were observed in 5-95% of participants. Fifty-nine antibodies were differentially abundant (FDR<0.05) pre-diagnosis vs. post-diagnosis (Fig. 2), 14 of which (24%) were previously reported as IBD-specific1. Thirteen were more (22%) and 46 less (78%) frequently observed post-diagnosis. Those developing UC exhibited 33 differentially abundant antibody responses, while those with CD exhibiting only four (FDR<0.05). Individuals developing IBD exhibited lower frequencies of antibody responses against EBV-associated peptides post-diagnosis, e.g. Epstein-Barr nuclear antigen-1 (EBNA-1) and capsid protein V26, and varicella-zoster virus, alongside higher antibody responses against bacterial flagellins. Individuals developing UC showed elevated antibody responses mainly against viruses (e.g. human adenovirus C, enteroviruses B/C) and particular pathogenic bacterial species (e.g. pneumococcal histidine triad proteins) post-diagnosis compared to pre-diagnosis. Conclusion Distinct antibody responses appear years before IBD diagnosis, indicating potential involvement in pre-clinical disease development. Furthermore, post-diagnosis, lower frequencies of antibody responses against EBV may suggest reduced immunogenicity against this virus in early disease pathogenesis. 1. Bourgonje et al. Immunity. 2023.

What Does Atypical Chronic Lymphocytic Leukemia Really Mean? A Retrospective Morphological and Immunophenotypic Study.

Atypical chronic lymphocytic leukemia (CLL) is still defined according to morphological criteria. However, deviance from the typical surface immunological profile suggests an atypical immunological-based CLL. A large cohort of patients with CLL was retrospectively evaluated aiming at assessing morphological (FAB criteria), immunophenotypical (two or more discordances from the typical profile), and clinical-biological features of atypical CLL. Compared to typical cases, morphologically atypical CLL showed a greater percentage of unmutated IgVH and CD38 positivity, and a higher expression of CD20. Immunophenotypically atypical CLL was characterized by more advanced clinical stages, higher expression of CD20, higher rate of FMC7, CD79b and CD49d positivity, and by an intermediate-high expression of membrane surface immunoglobulin, compared to typical cases. When patients were categorized based on immunophenotypic and morphologic concordance or discordance, no difference emerged. Finally, morphological features better discriminated patients' prognosis in terms of time-to-first treatment, while concordant atypical cases showed overall a worse prognosis. Discordant cases by immunophenotype and/or morphology did not identify specific prognostic groups. Whether-in the era of molecular markers used as prognostic indicators-it does make sense to focus on morphology and immunophenotype features in CLL is still matter of debate needing further research.

Re-N-acetylation of group B Streptococcus type Ia capsular polysaccharide improves the immunogenicity of glycoconjugate vaccines

The capsular polysaccharides (CPS) of Group B Streptococcus play a crucial role as virulence determinants and are potential candidates for antigenic components in vaccine formulations. Alkaline treatments are commonly used to extract polysaccharides owing to their efficiency and cost-effectiveness; however, they may induce the removal of N-acetyl groups from CPS. This study involved re-N-acetylation of CPS Ia to improve its biological functionality. The structural modifications and enhanced antigenicity of CPS Ia were observed after re-N-acetylation. The tetanus toxoid (TT) was conjugated with either partially de-N-acetylated or fully re-N-acetylated CPS. As a result, the conjugate containing re-N-acetylated CPS (IaReN-TT) enhanced the induction of IgG antibody levels and functional antibodies in mice. Both passive and active protection assays substantiated the superior protective efficacy of IaReN-TT, suggesting that the re-N-acetylation of CPS Ia could be a critical step in refining the immunogenic profile of glycoconjugate vaccines.

Chimerism of avian IgY-scFv and truncated IgG-Fc: A novel strategy in cross-species antibody generation and enhancement.

Chicken single-chain fragment variable (IgY-scFv) is a functional fragment and an emerging development in genetically engineered antibodies with a wide range of biomedical applications. However, scFvs have considerably shorter serum half-life due to the absence of antibody Fc region compared with the full-length antibody, and usually requires continuous intravenous administration for efficacy. A promising approach to overcome this limitation is to fuse scFv with immunoglobulin G (IgG) Fc region, for better recognition and mediation by the neonatal Fc receptor (FcRn) in the host. In this study, engineered mammalian ΔFc domains (CH2, CH3, and intact Fc region) were fused with anti-canine parvovirus-like particles avian IgY-scFv to produce chimeric antibodies and expressed in the HEK293 cell expression system. The obtained scFv-CH2, scFv-CH3, and scFv-Fc can bind with antigen specifically and dose-dependently. Surface plasmon resonance investigation confirmed that scFv-CH2, scFv-CH3, and scFv-Fc had different degrees of binding to FcRn, with scFv-Fc showing the highest affinity. scFv-Fc had a significantly longer half-life in mice compared with the unfused scFv. The identified ΔFcs are promising for the development of engineered Fc-based therapeutic antibodies and proteins with longer half-lives. The avian IgY-scFv-mammalian IgG Fc region opens up new avenues for antibody engineering, and it is a novel strategy to enhance the rapid development and screening of functional antibodies in veterinary and human medicine.

The dengue-specific immune response and antibody identification with machine learning

Dengue virus poses a serious threat to global health and there is no specific therapeutic for it. Broadly neutralizing antibodies recognizing all serotypes may be an effective treatment. High-throughput adaptive immune receptor repertoire sequencing (AIRR-seq) and bioinformatic analysis enable in-depth understanding of the B-cell immune response. Here, we investigate the dengue antibody response with these technologies and apply machine learning to identify rare and underrepresented broadly neutralizing antibody sequences. Dengue immunization elicited the following signatures on the antibody repertoire: (i) an increase of CDR3 and germline gene diversity; (ii) a change in the antibody repertoire architecture by eliciting power-law network distributions and CDR3 enrichment in polar amino acids; (iii) an increase in the expression of JNK/Fos transcription factors and ribosomal proteins. Furthermore, we demonstrate the applicability of computational methods and machine learning to AIRR-seq datasets for neutralizing antibody candidate sequence identification. Antibody expression and functional assays have validated the obtained results.

Comparison of Measurable Residual Disease in Pediatric B-Lymphoblastic Leukemia Using Multiparametric Flow Cytometry and Next-Generation Sequencing.

Measurable residual disease (MRD) testing, a standard procedure in B-lymphoblastic leukemia (B-ALL) diagnostics, is assessed using multiparametric flow cytometry (MFC) and next-generation sequencing (NGS) analysis of immunoglobulin gene rearrangements. We evaluated the concordance between eight-color, two-tube MFC-MRD the LymphoTrack NGS-MRD assays using 139 follow-up samples from 54 pediatric patients with B-ALL. We also assessed the effect of hemodilution in MFC-MRD assays. The MRD-concordance rate was 79.9% (N=111), with 25 (18.0%) and 3 (2.2%) samples testing positive only by NGS-MRD (MFC-NGS+MRD) and MFC-MRD (MFC+NGS-MRD), respectively. We found a significant correlation in MRD values from total nucleated cells between the two methods (r=0.736 [0.647-0.806], P<0.001). The median MRD value of MFC-NGS+MRD samples was estimated to be 0.0012% (0.0001%-0.0263%) using the NGS-MRD assays. Notably, 14.3% of MFC-NGS+MRD samples showed NGS-MRD values below the limit of detection in the MFC-MRD assays. The percentages of hematogones detected in MFC-MRD assays significantly differed between the discordant and concordant cases (P<0.001). MFC and NGS-MRD assays showed relatively high concordance and correlation in MRD assessment, whereas the NGS-MRD assay detected MRD more frequently than the MFC-MRD assay in pediatric B-ALL. Evaluating the hematogone percentages can aid in assessing the impact of sample hemodilution.

Recurrent Genital Herpes and Balanoposthitis Candidiasis in Men with Incomplete Circumcision: A Case Report

Background: Circumcision can reduce the risk of sexually transmitted diseases (STDs). It may reduce males acquiring HSV-2 by 30% and 68% lower prevalence of balanitis than uncircumcised males. There is no report of incomplete circumcision as a risk for STD infection.&#x0D; Case presentation: A 31-year-old male complained of multiple ulcers that covered a yellowish crust on the penile with a burning sensation since 7 days ago. Initially, it was vesicles that turned into ulcers. One month ago, he complained of moist scales on his preputium that felt itchy and smelly. The patient is married and sexually active. History of intercourse with female sex workers without condoms 2 weeks ago. The patient had incomplete circumcision when he was a child; the preputium is still persistent and seldom cleaned regularly. One year ago, there was a history of vesicles on the penis. Physical examination revealed obesity grade 2. Venereological findings showed a whitish pseudo-membrane on the preputium, glans penis, and ulcers in various sizes covered pseudo-membrane surrounded erythema oedema. Laboratory revealed positive IgG HSV1, IgM, and IgG HSV2. A fungal culture is positive candida. Diagnosis established as recurrent genital herpes, balanoposthitis candidiasis, non-specific genital infection, candidiasis intertrigo. The patient has persistent preputium as the entry of commensal pathogens through abrasions in the mucosa, which causes infection. The patient had complete resolution after being administered oral acyclovir, doxycycline, and topical miconazole.&#x0D; Conclusion: Persistent preputium in incomplete circumcision is a risk for developing candidiasis, balanoposthitis, and recurrent genital herpes.

Prediction of antigen-responding VHH antibodies by tracking the evolution of antibody along the time course of immunization.

Antibody maturation is the central function of the adaptive immune response. This process is driven by the repetitive selection of mutations that increase the affinity toward antigens. We hypothesized that a precise observation of this process by high-throughput sequencing along the time course of immunization will enable us to predict the antibodies reacting to the immunized antigen without any additional in vitro screening. An alpaca was immunized with IgG fragments using multiple antigen injections, and the antibody repertoire development was traced via high-throughput sequencing periodically for months. The sequences were processed into clusters, and the antibodies in the 16 most abundant clusters were generated to determine whether the clusters included antigen-binding antibodies. The sequences of most antigen-responsive clusters resembled those of germline cells in the early stages. These sequences were observed to accumulate significant mutations and also showed a continuous sequence turnover throughout the experimental period. The foregoing characteristics gave us >80% successful prediction of clusters composed of antigen-responding VHHs against IgG fragment. Furthermore, when the prediction method was applied to the data from other alpaca immunized with epidermal growth factor receptor, the success rate exceeded 80% as well, confirming the general applicability of the prediction method. Superior to previous studies, we identified the immune-responsive but very rare clusters or sequences from the immunized alpaca without any empirical screening data.

Production and characterization of single-chain variable fragment antibodies targeting the breast cancer tumor marker nectin-4.

Nectin-4 is a novel biomarker overexpressed in various types of cancer, including breast cancer, in which it has been associated with poor prognosis. Current literature suggests that nectin-4 has a role in cancer progression and may have prognostic and therapeutic implications. The present study aims to produce nectin-4-specific single-chain variable fragment (scFv) antibodies and evaluate their applications in breast cancer cell lines and clinical specimens. We generated recombinant nectin-4 ectodomain fragments as immunogens to immunize chickens and the chickens' immunoglobulin genes were amplified for construction of anti-nectin-4 scFv libraries using phage display. The binding capacities of the selected clones were evaluated with the recombinant nectin-4 fragments, breast cancer cell lines, and paraffin-embedded tissue sections using various laboratory approaches. The binding affinity and in silico docking profile were also characterized. We have selected two clones (S21 and L4) from the libraries with superior binding capacity. S21 yielded higher signals when used as the primry antibody for western blot analysis and flow cytometry, whereas clone L4 generated cleaner and stronger signals in immunofluorescence and immunohistochemistry staining. In addition, both scFvs could diminish attachment-free cell aggregation of nectin-4-positive breast cancer cells. As results from ELISA indicated that L4 bound more efficiently to fixed nectin-4 ectodomain, molecular docking analysis was further performed and demonstrated that L4 possesses multiple polar contacts with nectin-4 and diversity in interacting residues. Overall, the nectin-4-specific scFvs could recognize nectin-4 expressed by breast cancer cells and have the merit of being further explored for potential diagnostic and therapeutic applications.

High-resolution snapshots of antibody repertoires as potential correlates of protection

High-resolution snapshots of antibody repertoires as potential correlates of protection Klaus Eyer from ETH Zurich describes high-resolution snapshots of antibody repertoires as potential correlates of protection. The induction and long-term presence of key adaptive immune cells are essential for vaccine-mediated protection. As a direct, causal measure of protection is often challenging; finding and defining correlates of protection are critical for vaccine development, approval, and efficacy testing. Correlates of protection are quantifiable signs of being protected from becoming infected and/or developing disease that may be causal to protection itself. Antibodies in serum are often assessed as potential correlates as immunisations often lead to generating a vaccine-specific, functionally active and diverse antibody repertoire. In its simplest form, a potential correlate could be their presence if binding by the antibody is sufficient. This is assessed in the so-called titer measurements. Here, a serum sample is sequentially diluted, and the binding of the antibodies towards the vaccine is evaluated and compared to an often empirically derived threshold. This gold-standard measure has many advantages: it is fast, reliable and easily compared.

Antithyroid antibody profile and viral markers in autoimmune thyroiditis in Chennai population

Autoimmune thyroid disease (AITD) is the result of a complex interaction between genetic and environmental factors, which leads to failure of one or more mechanisms responsible for controlling thyroid-reactive T and B cells. The most frequently occurring clinical forms of autoimmune thyroiditis include Hashimoto’s thyroiditis and Grave’s disease. Viruses have been implicated in the onset of autoimmune disorders. This study aims to investigate the association between and in autoimmune thyroiditis by assessing virologic and immunologic parameters of cases with clinical indication of AITD. Anti-thyroid peroxidase (TPO) and Anti-thyroglobulin (TG) antibodies were evaluated using ELISA. The presence of Hepatitis C virus (HCV) IgG antibodies and IgM antibodies were evaluated using ELISA. The presence of RNA was investigated by RT-PCR. A total of sixty study subjects were involved in this study. Sixteen male patients (26.66%) and forty-four female patients (68.33%) were positive for Anti-TPO antibodies. Four male patients (6.66%) and twenty-five female patients (41.66%) were positive for Anti-TG antibodies. Four male patients (6.66%) and twenty-two female patients (36.66%) were positive for both Anti-TPO and Anti-TG antibodies. One female patient tested positive for HCV IgG antibodies. Sixteen patients (26.66%) were positive for IgM by ELISA of which 3 patients (5%) were male and 13 patients (21.66%) were female. None of the samples were positive for RNA. We conclude that viral infection may be involved in triggering autoimmune mechanisms. Further studies with a larger population are necessary to establish an association between HCV, and in the pathogenesis of autoimmune thyroid disorders.

A Case of Retinal Edema in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis

Purpose: To report a case of retinal edema and retinal hemorrhage in myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG) positive optic neuritis.Case summary: A 49-year-old male visited the clinic due to decreased vision and eye pain in the left eye after 2 times of right eye and 1 time of left eye optic neuritis. The patient presented with eyelid swelling and retinal hemorrhage as well as optic disc swelling of the left eye. Optical coherence tomography (OCT) showed parafoveal intraretinal fluid. The patient received the intravenous high-dose steroids and the immune globulin therapy. He was then put on maintenance oral steroids and immunosuppressive agents. After the treatment, the best corrected visual acuity of left eye was improved to 0.2. Retinal hemorrhage and retinal edema of the left eye decreased, and optic nerve pale in both eyes was observed. OCT showed overall atrophy of the retinal nerve fiber layer in both eyes.Conclusions: Some patient with MOG-IgG positive optic neuritis will have eyelid swelling or retinal edema that is necessary to be differentiated from eyelid inflammatory disorder or macular disease such as diabetic retinopathy. Thus, clinician should consider MOG-IgG positive optic neuritis in patients with retinal edema when accompanied by eye pain with severe vision loss or repeated disc swelling. When diagnosed with MOG-IgG positive optic neuritis, a combined treatment of relatively long-term steroid treatment and immunosuppressants may be required.

Experience with 23-valent pneumococcal polysaccharide vaccine in patients with ankylosing spondylitis and psoriatic arthritis

Pneumococcus plays a primary role as a causative agent of pneumonia both in the general population and in patients with immuno-inflammatory rheumatic diseases (IVRS), including spondylarthritis (SpA). However, data on the immunogenicity, efficacy and safety of pneumococcal vaccines in patients with SpA are limited.The aim of the study. To study the immunogenicity, efficacy and safety of the 23-valent pneumococcal polysaccharide vaccine (PPV-23) in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA), observed at the V.A. Nasonova Research Institute (Moscow, Russia).Materials and methods. 145 people were included in the study: 51 patients with AS, 25 with PsA, 69 in control group (СG) without IVR. The majority of patients (65.8%) received immunosuppressive therapy. PPV-23 was administered in an amount of one dose (0.5 ml) subcutaneously against the background of antirheumatic therapy, regardless of the activity of the main IVR. The level of antibodies (AT) to pneumococcal capsular polysaccharide was determined using the EIA PCP IgG kit (TestLine Clinical Diagnostics, Czech Republic) before vaccination and 1, 3 and 12 months after it. The clinical efficacy and safety of PPV-23 were also evaluated, including the effect on the activity of AS and PsA according to the dynamics of BASDAI and DAPSA indices.Results. After 1, 3 and 12 months after vaccination, the concentration of pneumococcal AT was significantly higher compared to baseline values, which indicates sufficient immunogenicity of PPV-23. The clinical efficacy of PPV-23 in patients with AS and PsA was 98.7%. In general, there was no negative effect of vaccination on the activity of the underlying disease. The frequency of postvaccinal reactions in patients and in СG was comparable.Conclusions. The obtained results of the study indicate sufficient immunogenicity, clinical efficacy and safety of PPV-23 in patients with AS and Ps A.