The importance of minimal residual disease for detection of late relapse in Bprecursor acute lymphoblastic leukemia.

BACKGROUND: The minimal residual disease (MRD) level in patients with B-precursor acute lymphoblastic leukemia (B-ALL) is the strongest independent predictor of relapse and survival. Assessment of MRD plays a crucial role in the treatment of B-ALL. CASE REPORT: We performed long-term monitoring of a 30-year-old woman with B-ALL of standard risk for MRD using multiparametric flow cytometry (MFC). After five years of monitoring, molecular relapse of the disease was confirmed. CONCLUSION: This case illustrates that more extended monitoring for MRD, even by only MFC when other newer sophisticated diagnostics are not available, is essential in detecting early relapse in patients with B-ALL of standard risk. HIPPOKRATIA 2022, 26 (1):38-40.

A pathogenetic role for the thymoma in myasthenia gravis. Autosensitization of IL-4- producing T cell clones recognizing extracellular acetylcholine receptor epitopes presented by minority class II isotypes.

Myasthenia gravis (MG) is caused by helper T cell-dependent autoantibodies against the muscle acetylcholine receptor (AChR). Thymic epithelial tumors (thymomas) occur in 10% of MG patients, but their autoimmunizing potential is unclear. They express mRNAs encoding AChR alpha and epsilon subunits, and might aberrantly select or sensitize developing thymocytes or recirculating peripheral T cells against AChR epitopes. Alternatively, there could be defective self-tolerance induction in the abundant maturing thymocytes that they usually generate. For the first time, we have isolated and characterized AChR-specific T cell clones from two MG thymomas. They recognize extracellular epitopes (alpha75-90 and alpha149-158) which are processed very efficiently from muscle AChR. Both clones express CD4 and CD8alpha, and have a Th-0 cytokine profile, producing IL-4 as well as IFN-gamma. They are restricted to HLA-DP14 and DR52a; expression of these minority isotypes was strong on professional antigen-presenting cells in the donors' tumors, although it is generally weak in the periphery. The two clones' T cell receptor beta chains are different, but their alpha chain sequences are very similar. These resemblances, and the striking contrasts with T cells previously cloned from non-thymoma patients, show that thymomas generate and actively induce specific T cells rather than merely failing to tolerize them against self antigens.

Detection of alpha-subunit isoforms in human muscle acetylcholine receptor by specific T cells from a myasthenia gravis patient.

The nicotinic acetylcholine receptor (AChR) is both the best-characterized transmitter receptor-ion channel and the target for the pathogenic antibodies in the human autoimmune disease myasthenia gravis (MG). In cloning and sequencing its components in man, we found that the alpha-subunit was transcribed in two isoforms, with (P3A+) or without (P3A-) a 75 base pair exon that had not been described in other species. While studying the human T lymphocyte response to recombinant AChR, we found that part of this P3A insert was recognized by one T cell line (from an MG patient), whereas another line only recognized the uninterrupted insertion site. To establish whether this exon is also translated in normal human muscle, we initially raised anti-peptide antibodies to the relevant amino acid sequences, but these failed to bind native AChR (affinity-purified from muscle on alpha-neurotoxin columns). We therefore exploited the great sensitivity and specificity of these T cells to detect the two isoforms after unfolding by antigen-presenting cells, and have been able to show that both are expressed in affinity-purified human muscle AChR.