Molecular analysis of antigen receptor variable region repertoires in T lymphocytes infiltrating the intrathyroidal and extrathyroidal manifestations in patients with Graves' disease<sup>*</sup>
Bibliographic record
Abstract
To determine whether T cells infiltrating thyroid, orbital and pretibial tissue of patients with Graves' ophthalmopathy (GO) and pretibial dermopathy (PTD) represent a primary immune response that is directed against certain antigenic determinants shared between these involved tissues, we characterized these T cells at the molecular level. T cell antigen receptor (TcR) variable (V) region gene usage in thyroid, orbital, pretibial tissue and peripheral blood mononuclear cells of patients with GD, GO and PTD was assessed using RT-PCR and 22 Vα and 23 Vß gene-specific oligonucleotide primers, followed by Southern hybridization analysis using TcR C-re-gion-specific, digoxigenin-labelled oligonucleotide probes. In some instances, CDR3- and junctional regions of TcR Vß genes were sequenced. Marked restriction and similarities of Vα and Vß gene usage were detected in samples derived from patients with active GO and PTD of recent onset. Moreover, sequence analysis of junctional domains of Vß families revealed oligo-clonality of some intrathyroidal, orbital and pretibial T cell populations as well as the presence of conserved junctional motifs shared by T cells derived the thyroid gland and the extrathyroidal sites. These data suggest that similar antigenic determinants may be responsible for the recruitment and oligoclonal expansion of T cells both within the thyroid gland and at the involved extrathyroidal sites in Graves' disease. Zusammenfassung Wir untersuchten, ob die in das Schilddrüsen-, Orbital- und Prätibialgewebe von Patienten mit Morbus Basedow, endokriner Orbitopathie (EO) und prätibia-lem Myxödem (PTM) infiltrierenden Lymphozyten eine primäre Immunantwort reflektieren, die gegen ein begrenztes Spektrum gemeinsamer antigener Determinanten gerichtet ist. Die molekulare Charakterisierung der variablen Regionen der T-Zell-Antigenrezeptoren (TcR) erfolgte mittels RT-PCR und 22 Vα und 23 Vß-Gen-spezifischen Primerpaaren, gefolgt von Southern-Hybridisierungen mit Digoxigenin-markierten, für die konstante Region des TcR spezifischen Oligonukeotid-Sonden. Bei 2 Patienten mit aktiver EO und PTM wurden die CDR-3- und junktionalen Regionen der TcR ß-Ketten sequenziert. Bei Patienten mit aktiven Manifestationen zeigten sich eine erhebliche Restriktion und phnlichkeiten der intrathyreo-idalen, orbitalen und prätibialen TcR Vα und Vß-Gen-Reper-toires bezüglich V-Gen-Gebrauch und Restriktionsgrad. Die Sequenzanalyse der junktionalen Regionen dominierender Vß-Genfamilien ergab für eine Reihe intrathyreoidaler, orbitaler und prätibialer T-Zell-Populationen den Nachweis der Oligo-klonalität sowie zahlreicher konservierter junktionaler Motive. Diesen Befunden zufolge dürften ähnliche antigene Determinanten im thyreoidalen und extrathyreoidalen Gewebe für die Rekrutierung und oligoklonale Expansion von T-Zellen bei Patienten mit Morbus Basedow, EO und PTM verantwortlich sein.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".