Antibody rejection is often accompanied by non-donor HLA specific antibodies (NDSA) and self-reactive antibodies that develop alongside donor-specific antibodies (DSA). To determine the source of these antibodies, we immortalized 107 B cell clones from a kidney transplant recipient with humoral rejection. Two of these clones reacted to HLA class I or MICA. Both clones were also reactive to self antigens and a lysate of a kidney cell line, hence revealing a pattern of polyreactivity. Monoclonality was verified by the identification of a single rearranged immunoglobulin heavy chain variable region (VH) sequence for each clone. By tracking their unique CDR3 sequence, we found that one such polyreactive clone was highly expanded in the patient blood, representing ~0.2% of circulating B cells. The VH sequence of this clone showed evidence of somatic mutations that were consistent with its memory phenotype and its expansion. Lastly, the reactivity of the expanded polyreactive B cell clone was found in the patient serum at time of rejection. In conclusion, we provide here proof of principle at the clonal level that human antibodies can cross-react to HLA and self. Our findings strongly suggest that polyreactive antibodies contribute to DSA, NDSA as well as autoantibodies, in transplant recipients.

One in 5,000 to 1 in 50,000 births have multiple endocrine neoplasia type 1 (MEN1). MEN1 is a hereditary syndrome clinically defined by the presence of two of the following endocrine tumors in the same patient: parathyroid adenomas, entero-pancreatic endocrine tumors and pituitary tumors. Most commonly, patients with MEN1 manifest primarily with signs and symptoms linked to primary hyperparathyroidism. By age 50, it is estimated that 100% of patients with MEN1 will have been diagnosed with primary hyperparathyroidism. These patients will need to undergo resection of their hyperfunctioning glands, however there is no clear consensus on which procedure to perform and when to perform it in these patients. In this original study we describe and explain the rational of our peri-operative approach and management at MD Anderson Cancer Center of MEN1 patients with hyperparathyroidism. This protocol includes preoperative evaluation, intraoperative decision-making and detailed surgical technique adopted for these patients' care. Additionally we review follow-up and disease management in instances of recurrent primary hyperparathyroidism in patients with MEN1 syndrome.

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