RESUMO
The vertebrate adaptive immune system modifies the genome of individual B cells to encode antibodies that bind particular antigens1. In most mammals, antibodies are composed of heavy and light chains that are generated sequentially by recombination of V, D (for heavy chains), J and C gene segments. Each chain contains three complementarity-determining regions (CDR1-CDR3), which contribute to antigen specificity. Certain heavy and light chains are preferred for particular antigens2-22. Here we consider pairs of B cells that share the same heavy chain V gene and CDRH3 amino acid sequence and were isolated from different donors, also known as public clonotypes23,24. We show that for naive antibodies (those not yet adapted to antigens), the probability that they use the same light chain V gene is around 10%, whereas for memory (functional) antibodies, it is around 80%, even if only one cell per clonotype is used. This property of functional antibodies is a phenomenon that we call light chain coherence. We also observe this phenomenon when similar heavy chains recur within a donor. Thus, although naive antibodies seem to recur by chance, the recurrence of functional antibodies reveals surprising constraint and determinism in the processes of V(D)J recombination and immune selection. For most functional antibodies, the heavy chain determines the light chain.
Assuntos
Anticorpos , Seleção Clonal Mediada por Antígeno , Cadeias Pesadas de Imunoglobulinas , Cadeias Leves de Imunoglobulina , Animais , Sequência de Aminoácidos , Anticorpos/química , Anticorpos/genética , Anticorpos/imunologia , Antígenos/química , Antígenos/imunologia , Linfócitos B/citologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Regiões Determinantes de Complementaridade/química , Regiões Determinantes de Complementaridade/imunologia , Cadeias Pesadas de Imunoglobulinas/química , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/imunologia , Mamíferos , Cadeias Leves de Imunoglobulina/química , Cadeias Leves de Imunoglobulina/genética , Cadeias Leves de Imunoglobulina/imunologia , Memória Imunológica , Recombinação V(D)J , Seleção Clonal Mediada por Antígeno/genética , Seleção Clonal Mediada por Antígeno/imunologiaRESUMO
PURPOSE: To evaluate cardiac MRI characteristics in patients with suspected hypersensitivity myocarditis following mRNA COVID-19 vaccination. MATERIALS AND METHODS: Patients clinically suspected of acute myocarditis after COVID-19 vaccination were retrospectively analyzed and compared against a healthy control group.âCardiac MRI protocol included parameters such as T1 and T2 relaxation times, extracellular volume (ECV), T2 signal intensity ratio, and late gadolinium enhancement (LGE). Lymph node size was assessed in the patient group on the injection side. Student t-test, analyses of variance (ANOVA) with Tukey post-hoc test, and χ2 test were used for statistical analysis. RESULTS: 20 patients with clinically suspected post-vaccine myocarditis (28â±â12 years; 12 men) and 40 controls (31â±â11 years; 25 men) were evaluated. According to the 2018 Lake Louise criteria (LLC), patients with clinically suspected myocarditis were further subdivided into an LLC-positive group (nâ=â9) and an LLC-negative group (nâ=â11). The mean time of symptom onset after vaccination was 1.1â±â1.2 days (LLC-positive) and 6.5â±â9.2 days (LLC-negative). Group differences in inflammatory variables between myocarditis patients and control subjects were more pronounced in the LLC-positive group (e.âg., T1 relaxation time: 1041â±â61âms [LLC positive] vs. 1008â±â79âms [LLC-negative] vs. 970â±â25âms [control]; pâ<.001; or T2 signal intensity ratio 2.0â±â0.3 vs. 1.6â±â0.3 [LLC-negative] and vs. 1.6â±â0.3 [control], pâ=â.012). LLC-positive patients were significantly faster in receiving an MRI after initial symptom onset (8.8â±â6.1 days vs. 52.7â±â33.4 days; pâ=â.001) and had higher troponin T levels (3938â±â5850âng/l vs. 9â±â11âng/l; pâ<.001). LGE lesions were predominantly located at the subepicardium of the lateral wall. Axillary lymphadenopathy was more frequent in the LLC-positive group compared to the LLC-negative group (8/9 [89â%] vs. 0/11 [0â%], pâ<â0.001). CONCLUSION: Vaccine-induced myocarditis should be considered in patients with acute symptom onset after mRNA vaccination, especially if elevated serum troponin T is observed. Imaging findings of vaccine-induced myocarditis are similar to virus-induced myocarditis, allowing for the use of the Lake Louise Criteria for diagnostic purposes. KEY POINTS: · Vaccine-induced hypersensitivity myocarditis can be confirmed with cardiac MRI. · Especially patients with sudden onset of symptoms and elevated serum troponin T had positive cardiac MRI findings. · Cardiac MRI characteristics of vaccine-induced myocarditis are similar to those in virus-induced myocarditis. CITATION FORMAT: · Kravchenko D, Isaak A, Mesropyan N etâal. Cardiac MRI in Suspected Acute Myocarditis After COVID-19 mRNA Vaccination. Fortschr Röntgenstr 2022; 194: 1003â-â1011.