SFEBES2017 Poster Presentations Thyroid (38 abstracts)
Autoantibodies to the thyrotropin receptor in Alemtuzumab-induced thyroid autoimmunity: determination of their biological activity, and possible role as predictive marker of disease
Ilaria Muller 1 , Mark Willis 2 , Sarah Healy 2 , Taha Nasser 2 , Lei Zhang 1 , Mohd Shazli Draman 1 , Peter Taylor 1 , Neil Robertson 2 , Marian Ludgate 1 & Colin Dayan 1
1Thyroid Research Group, Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, UK; 2Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
Background: Alemtuzumab (ALTZ) is a humanised monoclonal anti-CD52 antibody used as effective treatment for relapsing/remitting multiple sclerosis (MS), causing panlymphopenia with subsequent lymphocyte repopulation. Unfortunately, around 40% of patients develop secondary humoral autoimmunity, mainly affecting the thyroid gland. Anti-thyrotropin-receptor (TSHR) autoantibodies (TRAb) can stimulate (TSAb), block (TBAb) or not affect (‘neutral’) TSHR function, with TSAb causing hyperthyroid Graves’ disease (GD), and TBAb hypothyroidism. Low-affinity neutral TRAb could pre-exist in MS patients, then undergo somatic hypermutation to become high-affinity TSAb/TBAb post-ALTZ, causing thyroid dysfunction.
Methods: Sera from MS patients, 11 developing post-ALTZ thyroid autoimmunity (TA; 10 GD, 1 hypothyroidism) and 14 not developing it (NO-TA), were obtained from the Welsh Neuroscience Research Tissue Bank (Cardiff, UK), and evaluated at different time-points: (1) pre-ALTZ, (2) post-ALTZ before the disease onset (TA) or latest time post-ALTZ (NO-TA), (3) post-ALTZ during/after thyroid dysfunction onset (TA only). Flow cytometry (FC) detected any TSHR-binding TRAb. Luciferase bioassays (LB) detected both TRAb presence and bioactivity (neutral/TSAb/TBAb), also deduced from the corresponding thyroid function. TRAb positivity (TRAb+) was defined as FC and/or LB assays positivity.
Results: Among overall TRAb+ cases (all time-points considered), TBAb were 2/7 (28.6%) in GD, 1/1 (100%) in hypothyroidism, and 3/4 (75%) in NO-TA.
Conclusions: (A) Patients with positive TRAb prior to ALTZ had an increased tendency to develop post-treatment TA. Thus baseline TRAb could provide a predictive marker of future development of thyroid dysfunction. (B) TRAb+ patients were euthyroid at time-points 1–2, suggesting the presence of low-affinity antibodies unable to affect thyroid function. (C) Post-ALTZ TBAb subtype is common, and could be responsible for post-ALTZ hypothyroidism, and cases of post-ALTZ Graves’ disease with fluctuating thyroid function.
| Time- points | TRAb+ | Fisher Exact T-test | |
| TA | NO-TA | ||
| 1 | 3/11 (27.3%) | 0/14 (0%) | P=0.07 |
| 1+2 | 5/11 (45.5%) | 4/14 (28.6%) | P=0.43 |
| 3 | 8/11 (72.7%) | NA | NA |
| NA=Not Applicable. | |||
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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