Dataset Information

Clonal diversification in OspA-specific antibodies from peripheral circulation of a chronic Lyme arthritis patient.

ABSTRACT: Chronic, antibiotic treatment-resistant Lyme arthritis develops in a subset of patients following infection with the tick-borne spirochete Borrelia burgdorferi and persists after apparent microbial clearance. IgG responses to Outer Surface Protein (Osp) A, an abundant spirochetal lipoprotein, correlate with both severity and duration of joint inflammation. Characterization of this OspA-directed antibody response is, therefore, important for understanding some of the mechanisms that sustain persistent pathology. Such analyses in Lyme arthritis patients have been previously hampered by relatively small amounts of clinical blood samples, as well as the general intractability and low success rates of B-cell immortalization procedures. Here we describe a robust method for generation of OspA-specific monoclonal antibody fragments from archival cell samples employing a three-step procedure -- isolation of single OspA-specific B-cells, their ex vivo clonal expansion and production of expressed immunoglobulins as single chain variable region fragments (scFvs). Interestingly, two of three scFvs generated from a single patient were of a common clonal origin, additional somatic mutations in the downstream member resulting in a concomitant modulation of antigen binding affinity. Computational docking of OspA into corresponding Fv domains, generated by molecular modeling, reveals subtle binding site differences which could account for the observed alteration in ligand binding. Besides their utility as standards in routine diagnostic assays, being the first described OspA-specific human monoclonal reagents, these scFvs are useful tools for analysis of the anti-OspA repertoire in patients and for identification of putative human mimics of the bacterial protein.

SUBMITTER: Ghosh S

PROVIDER: S-EPMC1899465 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature

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Clonal diversification in OspA-specific antibodies from peripheral circulation of a chronic Lyme arthritis patient.

Ghosh Srimoyee S Huber Brigitte T BT

Journal of immunological methods 20070206 1-2

Chronic, antibiotic treatment-resistant Lyme arthritis develops in a subset of patients following infection with the tick-borne spirochete Borrelia burgdorferi and persists after apparent microbial clearance. IgG responses to Outer Surface Protein (Osp) A, an abundant spirochetal lipoprotein, correlate with both severity and duration of joint inflammation. Characterization of this OspA-directed antibody response is, therefore, important for understanding some of the mechanisms that sustain persi ...[more]

PMID: 17307198

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Project description:BackgroundHealthcare providers frequently struggle to provide effective care to patients with chronic Lyme-associated symptoms (chronic Lyme disease, CLD), potentially causing these patients to feel misunderstood or neglected by the healthcare system. This study is the first to use a combined medical and communication science approach, and aims to assess patients' experiences with CLD & CLD-related care, identify themes and repertories in these patients' narrations, and provide potential ways to improve communication with them.MethodsInformed by the principles of 'clean language', we conducted focus groups with self-identified CLD patients (N = 15). We asked participants about their experiences with CLD and CLD-related healthcare. We performed thematic analyses using a bottom-up approach based in discourse analysis. We also sought to identify specific types of verbalizations (repertoires) across themes.ResultsParticipants thematised a heterogeneous set of CLD-associated symptoms, which they frequently labelled as 'invisible' to others. Their illness significantly affected their daily lives, impacting their work, social activities, relationships with loved ones, hobbies and other means of participating in society. Negative experiences with healthcare providers were near-universal, also in patients with short-lived CLD-associated symptoms. Verbalizations were notable for frequent use of communicative modes that implicitly create common ground between participants and that give a certain validity to personal experiences (impersonal 'you' and other forms of presupposition).ConclusionCentral themes found in CLD patients' communication are 1. the experience of significant symptoms, 2. for which adequate relief is only rarely found from conventional medical practitioners, and 3. that are largely invisible to the outside world. Verbalizing these themes, patients use various repertoires for their shared experiences, such as a feeling of abandonment or not being heard by the medical system, feelings of loss with respect to their previous health, and the idea that they might have been better off had they been diagnosed sooner. Working with these repertoires will enable healthcare providers to establish a shared perspective with their CLD patients, thus engaging in more fruitful doctor-patient communication. We hypothesize that these findings are not unique to CLD, but may also be applicable to other conditions with an uncertain aetiology, such as Long COVID.

Dataset Information

Clonal diversification in OspA-specific antibodies from peripheral circulation of a chronic Lyme arthritis patient.

Publications

Clonal diversification in OspA-specific antibodies from peripheral circulation of a chronic Lyme arthritis patient.

Similar Datasets

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