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Dipeptidyl Peptidase IV

So far you will find no curative treatment modalities for this entity apart from bone marrow transplantation

So far you will find no curative treatment modalities for this entity apart from bone marrow transplantation. and is revealed early in life usually before 5?years of age. The mutation in most ALPS patients are in the gene encoding the lymphocyte protein FAS [3]. FAS are a receptor expressed on activated lymphocyte that mediates programmed cell death. These patients also have autoantibodies most often directed to reddish blood cells, neutrophils and platelets manifesting as hemolytic anemia, autoimmune neutropenia and immune thrombocytopenic purpura. ALPS patients have lymphocytosis and a number of lymphocyte abnormalities including marked growth of T lymphocytes that express alpha/beta T cell receptors but Rabbit Polyclonal to TK (phospho-Ser13) no CD4 and CD8 surface markers (TCR /+?CD4CCD8). Lymphoproliferation in ALPS patients BOC-D-FMK is generally benign, but they are at increased risk for developing Hodgkins and Non Hodgkins lymphoma. Definite treatment modalities have not been established so far. Varieties of immunosuppressive drugs have been tried. We successfully treated a patient with Mycophenolate Mofetil and weekly Pyrimethamine/Sulfadoxine (fancidar). Case Statement A 5-12 months 3-month-old girl given birth to to a non-consanguineous marriage presented with increasing pallor of one-month period, fever and right axillary swelling with history of having received two blood transfusions. She was also started on anti tuberculosis drugs prior to coming to our centre. She did not have family history of receiving blood transfusions or comparable illness in the family. On examination, she had severe pallor, moderate icterus, multiple cervical (2??2?cm), axillary (3.5??2??2?cm) lymphnodes, splenohepatomagaly (6 and 3.5?cm respectively) and protein energy malnutrition grade1. She experienced no evidence of cutaneous bleed and fundus was normal. BOC-D-FMK On investigation, lab studies revealed anemia (Hemoglobin 3.2?g%, reticulocytes 6.2%, total leucocyte count 3900/cumm, neutrophils 62%, lymphocyte 31%, monocyte 03%, eosinophil 02%, Platelets?=?3,33,000?cumm). Peripheral smear showed marked anisopoikilocytosis and polychromasia. Total Bilirubin 2.2?mg/dl, Direct bilirubin BOC-D-FMK 0.6?mg/dl. Direct Coombs test was positive (3+). Match levels, antinuclear antibody and anti double stranded DNA antibody were normal. Bone marrow smear and biopsy revealed megaloblastic switch in erythroids with myeloid maturation and adequate megakaryocytes. Lymphnode biopsy showed reactive hyperplasia. There were no abnormal cells in bone marrow or lymph node biopsy. Mantoux test was unfavorable and Chest X-ray was normal. Renal function test was also normal. HIV serology was non reactive and hepatitis B surface antigen & anti hepatitis C serology was unfavorable (Furniture?1, ?,22). Table?1 ALPS-features BOC-D-FMK Non malignant lymphoproliferation?Chronic splenomegaly?PolyadenopathiesAutoimmune manifestations [4, 5]?Hemolytic anemia?Thrombocytopenia?Neutropenia?Other Autoimmune manifestationBiological features?Hyper-IgG (Hyper IgA)?High number of BOC-D-FMK double unfavorable (TCR?+?T Cells in blood and lymphoid tissues)?AutoantibodiesFamily history?Lymphoproliferative syndrome?Autoimmune manifestationHistological features [6]?Reactive follicular hyperplasic and paracortical expansion with immunoblasts and plasma cells.?Splenic tissue from patients demonstrates lymphoid hyperplasia of the white pulp due to B cells expansion in the lymphoid follicles, while T cells accumulates is usually paracortical areas. Open in a separate window Table?2 Genes associated with ALPS [7] FAS (TNFR SF6)?ALPS0Homozygous in FAS?ALPS1Heterozygous FAS germline mutations, accounts for 75% of individuals with ALPS?ALPS 1A-SMSomatic mutations in selected cell populace, including/ DNT cells in individuals with ALPS with a phenotype similar to that caused by FAS germline mutationsFAS-LG (TNFR SF6)?ALPS 1Ban with germline mutations in FAS LGCASP-10?ALPS-11Homozygous and Heterozygous mutations in CASP-10Other loci?ALPS-111if all known genetic defects have been ruled out. Open in a separate window A diagnosis of autoimmune hemolytic anemia was made and she was initiated on Prednisolone (2?mg/kg) with no sustained response for 10?months. Subsequently, she developed to have Evans Syndrome suggested by the development of anti platelet antibodies. She continued to have recurrent relapses with partial response to intravenous Immunoglobulins and steroids. In view of persisting lymphadenopathy and splenohepatomegaly and autoimmune cytopenias, Immuno-phenotyping of peripheral blood was sent which revealed Double unfavorable T-cells of 4.88%, (Healthy Control 0.93%), CD3 52.4%, CD4 26.5%, CD8 21.9% and CD20 24.4% suggestive of ALPS. As she developed relapses on long term steroids, she was started on mycophenolate mofetil 250?mg (15?mg/kg) BD and Tab Pyrimethamine- sulfadoxine (25/200?mg) weekly for 4?weeks. On this treatment, she has shown very good response and has been transfusion independent for one and a half year. Conversation ALPS should be kept as important differential diagnosis in dealing a child with autoimmune hemolytic anemia, Evans syndrome, lymphadenopathy and splenohepatomegaly. So far you will find no curative treatment modalities for this entity apart from bone marrow transplantation. Initial line of treatment for most patients is usually either prednisolone alone or in combination with intravenous Immunoglobulin. Patients with immune cytopenia refractory to splenectomy and steroid treatment can be treated with variety of brokers including, cyclosporin A, vincristine methotrexate, azathioprine, mycophenolate [8], rituximab. Mycophenolate mofetil is derived from fungus em Penicillium stoloniferum /em . It inhibits inosine mono-phosphate dehyrogenase, the enzyme.