With the development of an insulin autoantibody (IAA) assay performed in 96-well filtration plates, we have evaluated prospectively the development of IAA in NOD mice (from 4 weeks of age) and children (from 7 to 10 months of age) at genetic risk for the development of type 1 diabetes. NOD mice had heterogeneous expression of IAA despite being inbred. IAA reached a peak between 8 and 16 weeks and then declined. IAA expression by NOD mice at 8 weeks of age was strongly associated with early development of diabetes, which occurred at 16 -18 weeks of age (NOD mice IAA ؉ at 8 weeks: 83% (5͞6) diabetic by 18 weeks versus 11% (1͞9) of IAA negative at 8 weeks; P < .01). In man, IAA was frequently present as early as 9 months of age, the first sampling time. Of five children found to have persistent IAA before 1 year of age, four have progressed to diabetes (all before 3.5 years of age) and the fifth is currently less than age 2. Of the 929 children not expressing persistent IAA before age 1, only one has progressed to diabetes to date (age onset 3), and this child expressed IAA at his second visit (age 1.1). In new onset patients, the highest levels of IAA correlated with an earlier age of diabetes onset. Our data suggest that the program for developing diabetes of NOD mice and humans is relatively ''fixed'' early in life and, for NOD mice, a high risk of early development of diabetes is often determined by 8 weeks of age. With such early determination of high risk of progression to diabetes, immunologic therapies in humans may need to be tested in children before the development of IAA for maximal efficacy.insulin autoantibodies ͉ radioassay ͉ type 1 diabetes T ype 1A diabetes mellitus, as defined by an expert panel of the American Diabetes Association, is characterized by the presence of antiislet autoantibodies (1). There has been tremendous progress in defining islet autoantigens and developing antiislet autoantibody assays (2-4). In the most recent Immunology of Diabetes Workshop, a series of antiislet autoantibody assays were compared (2). Although the GAD65 autoantibody (GAA) and ICA512 (IA-2) autoantibody (ICA512AA) assays showed good concordance between laboratories, the insulin autoantibody (IAA) assays were divergent, with marked differences between laboratories in sensitivity and specificity. In this workshop, many of the IAA assays utilizing Ͻ600 l of sera had sensitivities Ϸ1͞2 of those utilizing a larger volume of serum (2). It is likely that such marked differences in interlaboratory measurement of IAA and the technical difficulty of current assays contributes to differences in the reported importance of IAA for disease prediction.Despite the difficulties of IAA determination, a number of laboratories have routinely measured IAA with large sera volume assays for large series of patients followed to the development of diabetes. Studies from multiple countries have reported that IAA has an important role in diabetes prediction (5-8). Antiinsulin autoantibodies appear to be unique in that their levels are ...
Objectives To summarize cases submitted to the 2019 Society for Hematopathology/European Association for Haematopathology Workshop under the category of myeloid/lymphoid neoplasms with eosinophilia and PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2 rearrangements, focusing on recent updates and relevant practice findings. Methods The cases were summarized according to their respective gene rearrangement to illustrate the spectrum of clinical, laboratory, and histopathology manifestations and to explore the appropriate molecular genetic tests. Results Disease presentations were heterogeneous, including myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDSs), MDS/MPN, acute myeloid leukemia, acute B- or T-lymphoblastic lymphoma/acute lymphoblastic lymphoma (ALL/LBL), or mixed-lineage neoplasms. Frequent extramedullary involvement occurred. Eosinophilia was common but not invariably present. With the advancement of RNA sequencing, cryptic rearrangements were recognized in genes other than PDGFRA. Additional somatic mutations were more frequent in the FGFR1-rearranged cases. Cases with B-ALL presentations differed from Philadelphia-like B-ALL by the presence of an underlying MPN. Cases with FLT3 and ABL1 rearrangements could be potential candidates for future inclusion in this category. Conclusions Accurate diagnosis and classification of this category of myeloid/lymphoid neoplasms has important therapeutic implications. With the large number of submitted cases, we expand our understanding of these rare neoplasms and improve our ability to diagnose these genetically defined disorders.
In a large population with primary AID, azathioprine exposure was associated with a 7-fold risk for myeloid neoplasm. The control and case cohorts had similar systemic exposures by agent category. No association was found for anti-tumor necrosis factor agents. Finally, no timeline was found for the association of drug exposure with the incidence in development of myeloid neoplasm.
The loss of CD26 expression was proposed to be a constant feature of circulating Sézary cells by flow cytometric immunophenotyping (FCIP), but the experience with CD26 is limited. To establish its usefulness, CD26 results were correlated with morphologic, molecular, and immunophenotypic findings. Based on FCIP of 179 samples of peripheral blood, CD26 negativity was found in 59.3% of cases with Sézary syndrome (SS), 33.3% of mycosis fungoides (MF), 14.2% of benign dermatosis (BD), and no control cases. In diagnostic subgroups of SS based on morphologic, molecular, and immunophenotypic criteria, the percentage of CD26- cases varied from 41.1% to 63.6%. The specificity of a CD26- result was inferior to that of T-cell antigen loss in differentiating SS from MF and BD. CD26 offers lower diagnostic performance than previously suggested; however, in addition to the findings of major T-cell antigen loss, it could improve sensitivity of FCIP in patients with SS.
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