Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In patients with ALPS, defective homeostasis of lymphocytes is reflected in abnormal accumulation of lymphocytes, leading to lymphadenopathy, (hepato)splenomegaly and hypersplenism, autoimmunity due to a failure to remove autoreactive lymphocytes, and inappropriate survival of lymphocytes associated with an increased occurrence of lymphoma. Several of the laboratory findings are unique for ALPS and reflect defective Fas-mediated apoptosis and abnormal immune regulation. Much has been learned about the molecular mechanisms that underlie defective Fas-mediated apoptosis and the complex relationship between genotype, phenotype and disease penetrance. Family studies strongly suggest the contribution of one or more additional factors to the pathogenesis of ALPS. This may pertain to defective immunoregulation by an altered IL-2/IL-2 receptor system, reflected in the specific loss of CD4+/CD25+ T cells, and/or by the highly increased IL-10 levels, but other factors may equally be involved. Treatment strategies remain mostly targeted at the disease manifestations, but more specific therapies directed at the primary pathogenic defects themselves might become possible in the future. Continued efforts directed at both careful clinical follow-up and basic scientific investigation are needed to increase our understanding of the incidence, natural history, and pathogenesis of ALPS. In return, this may prove of benefit for the understanding of autoimmune disease in general.
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PMID:Autoimmune lymphoproliferative syndrome (ALPS). 1257 Aug 31

A 50-year-old man was admitted to another hospital with epigastralgia. Malignant lymphoma was suspected because the patient had increased levels of serum LDH and an abnormal Ga scintigraphy finding in his chest. When he was transferred to our hospital, he underwent a right inguinal lymphadenopathy. The laboratory data showed increased levels of serum LDH and soluble IL-2 receptor, but there was no appearance of peripheral abnormal lymphocytes. His chest MRI indicated tumors in the right atrium (4 cm x 4 cm) and in the head of his left humerus. Those tumors were enhanced by Gd-DTPA. There were no other lymphadenopathies. Histopathological and immunohistochemical studies showed T-cell type lymphoma in the right inguinal lymph node. Furthermore, monoclonal rearrangement of HTLV-I proviral DNA was detected from the lymph node by Southern blot analysis. Taken together, we diagnosed the patient as having ATL (lymphoma type). His condition has improved well with systemic chemotherapy. We report a rare case of lymphoma type ATL with initial massive cardiac involvement, although ATL cells sometimes involve the heart at the end of the disease course.
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PMID:[ATL (lymphoma type) presented with a mass formation in the heart]. 1260 95

A 54-year-old woman with a 21-year history of sarcoidosis was admitted to our hospital with dyspnea on exertion, weight loss, and the appearance of consolidation in chest radiographs. The serum level of soluble IL-2 receptor was high, and CT findings demonstrated mediastinal, hilar and abdominal lymphadenopathy. The histological findings of subpleural consolidation in a transbronchial lung biopsy of the left lung showed giant cells; and those of a CT-assisted biopsy of a retroperitoneal lymph node revealed non-caseous epithelioid cell granulomas. After the biopsy, severe thrombocytopenia (6,000/microliter) developed. With prednisolone treatment, the platelet count rose to normal and the subpleural consolidation on chest radiography was improved. Five weeks later, the had a productive cough with fever, rapidly progressive cavitary lesions and consolidation on chest radiography. Aspergillus fumigatus was detected in the sputum by PCR, and Aspergillus antigen was detected in the serum. She died of progressive respiratory failure, in spite of therapy with amphotericin B and itraconazole. We report a rare case of sarcoidosis and idiopathic thrombocytopenic purpura accompanied with invasive pulmonary aspergillosis.
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PMID:[A case of sarcoidosis and idiopathic thrombocytopenic purpura accompanied with invasive pulmonary aspergillosis]. 1269 45

We describe a case of hemophagocytic syndrome (HPS) associated with CD8-positive T-cell chronic lymphocytic leukemia (CD8 + T-CLL). A 68-year-old man with CD8 + T-CLL presented with fever, progressive pancytopenia, and lymphadenopathy. Laboratory findings showed a hyper-ferritinemia, abnormalities of coagulation tests, and liver and renal dysfunction with hypoproteinemia. He did not respond to any treatments and died of respiratory failure 10 days after the admission and 14 months after the onset of CD8 + T-CLL. Pathological findings of the autopsy demonstrated infiltration of CD8 + T-CLL cells in multiple organs along with the increase of histiocytes with prominent hemophagocytosis. Serum concentration levels of IL-6, soluble IL-2 receptor and VEGF were all elevated at admission. These findings revealed that he had a secondary HPS. It was suggested that HPS should be considered in patients with an unexplained cytopenia and a fever during the clinical course of CD8 + T-CLL.
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PMID:Hemophagocytic syndrome associated with CD8 positive T-cell chronic lymphocytic leukemia. 1506 Dec 21

A 24-year-old woman was referred to our hospital with fever and cervical lymphadenopathy. On admission, her serum concentration of soluble IL-2 receptor had increased to 1,740 IU/ml, LDH was 2,889 IU/l, and ferritin was 2,389 ng/ml. Dyspnea became evident (PaO2 60 Torr) with a further increase of serum ferritin to 96,552 mg/ml on day 11. Chest CT findings showed the thickening of the interlobular septa, bilateral pleural effusion, and swelling of mediastinal lymph nodes, symptoms which were very similar to those associated with lymphangitis carcinomatosis. She received steroid pulse therapy (methylprednisolone, 1,000 mg/day for three days). This resulted in a rapid improvement of her dyspnea and disappearance of the lymphatic blockade-mediated pulmonary findings in two days. A cervical lymph node biopsy was performed on day 12, and revealed that she had subacute lymphadenitis (Kikuchi disease). This case suggests that acute respiratory failure should be considered in cases of Kikuchi disease when associated with a lymphatic blockade.
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PMID:[Subacute necrotizing lymphadenitis showing lymphatic blockade-mediated acute respiratory failure]. 1678 97

A 48-year-old man infected with an HIV-1 experienced intermittent bouts of fever, lymphadenopathy, elevated CRP level, and thrombocytopenia, each lasting about 2 weeks, and recurring at 2-3 month intervals. His CD4 count was about 500/microL, and he had never received antiretroviral therapy (ART). In March 2005, he experienced the same symptoms, accompanied by liver damage, splenomegaly, pleural fluid, and a high serum soluble IL-2 receptor level. Examination of a cervical lymph node specimen resulted in a diagnosis of Castleman disease, plasma cell type. Immunohistochemical studies confirmed the presence of HHV-8 and Ebstein-Barr virus (EBV). Since the plasma HHV-8 DNA and serum IL-6 were elevated during the flare-up, were negative between episodes, he was treated with ART to control the Castleman disease. He remained asymptomatic for 3 months, but, similar symptoms recurred with a high level of HHV-8 DNA in his PBMCs. Oral valganciclovir was them started at 1,800 mg twice daily, and his symptoms immediately improved. The HHV-8 DNA level in the PBMCs decreased markedly over the course of 4 weeks, and valganciclovir was discontinued. One week later, he experienced another flare-up, and was successfully treated with 10 days of valganciclovir 1,800 mg, followed by maintenance with valganciclovir 900 mg. ART was discontinued, because the valganciclovir plus ART caused severe fatigue. No subsequent flare-ups have been observed, and, no HHV-8 DNA has been detected in his PBMCs. Castleman disease is an unusual complication in patients with HIV-1 and HHV-8 infection, but it should be included in the differential diagnosis of patients who exhibit a relapsing systemic inflammatory syndrome and lymphoadenopathy. Further study is needed to determine the appropriate usage and timing of the anti-HHV-8 and HIV-1 medication.
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PMID:[A case of HIV-1 and HHV-8-associated Castleman disease with a relapsing high fever and lymphoadenopathy]. 1692 87

We studied clinical manifestations, laboratory results, treatment, recurrence, and complications in 69 patients diagnosed with Kikuchi's disease by lymph node pathology from January 1, 1998, to December 31, 2007. Subjects were 34 men and 35 women (median age: 28 years, range: 12 to 58 years). Of the 69, 67 were Japanese and 2 were Korean. Major clinical symptoms and signs were fever >37 degrees (71%) and lymphadenopathy (100%). Lymphadenopathy was cervical in 93% and systemic in 3%. Some experienced night sweats and weight loss. The median white blood cell count was 3800 microL (1,700-9,300 microl), and 50.7% of subjects had leukocytopenia (<4,000 microL). The median serum LDH concentration was 245U/L (129-923 U/L). The median ferritin concentration, measured in 26 cases, was 769 ng/mL (4.5-2,580 ng/mL). The median concentration of soluble IL-2 receptor, measured in 27 cases, was 639 U/mL (0.5-4,000 U/ml). Having observed several cases with abnormally high ferritin and soluble IL2 receptor, we note the importance of carefully considering differential diagnosis from Still's disease and malignant lymphoma. Treatment included no medication in 30% of subjects, nonsteroidal anti-inflammatory drugs alone in 37.7%, steroids alone in 7%, and combined nonsteroidal anti-inflammatory drugs and steroids in 22%. Of the 29% administered steroids, we mostly used prednisolone (0.5-1.0 mg/kg), tapering the dose as clinical features improved. Two developed aseptic meningitis and 2 systemic lupus erythematosus. In total, 75% improved in less than 3 months, whereas 6% showed improvement only after at least 6 months of continued treatment. All were cured, but the condition recurred in 8%. Recurrence was not associated initial the disease duration. Recurrence cannot be predicted but can occur. In some cases, we could not distinguish lymphadenitis from malignant lymphoma or tuberculous lymphadenitis based on clinical features or laboratory data. Diagnosis must thus be based on lymph node pathology. We also must consider the possibility of recurrence or attacks of systemic lupus erythematosus.
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PMID:[Medical study of 69 cases diagnosed as Kikuchi's disease]. 1969 71

A-46-year-old woman admitted to our hospital because of numbness of bilateral lower limbs and urinary incontinence. The initial neurological examination showed sensory impairment below S1 level with urinary incontinence, indicating epicornus syndrome. Spinal MR imaging demonstrated unremarkable on conventional and enhanced images with Gd-DTPA. Cerebrospinal fluid examination revealed slightly elevated protein level without pleocytosis. Thereafter, subacute ascending myelopathy including flaccid paraparesis and urinary retention, developed. Because the patient had low grade fever, fatigue, weight loss and elevated serum soluble IL-2 receptor and LDH titers, we investigated her for lymphoma. Although lymphadenopathy or mass lesions were not found on whole-body CT scan, bone marrow biopsy showed the presence of inravascular large B-cell lymphoma (IVL). Thus the patient's progressive myelopathy was probably caused by IVL invasion. Ten days after the initiation of chemotherapy, her neurological symptoms transiently improved; however, her paraparesis and urinary incontinence gradually worsened thereafter, despite of treatment. IVL often presents with neurological manifestations, including myelopathy. There have been a few reports of IVL presenting with lower lumbar spinal cord and conus medullaris. It should be noted that IVL can cause unidentified progressive ascending myelopathy without positive MRI findings.
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PMID:[A case of intravascular malignant lymphomatosis presenting with epicornus syndrome and diagnosed by bone marrow biopsy]. 2029 32

Advanced-stage primary cutaneous T-cell lymphoma has an unfavorable prognosis and low survival rates. Aggressive treatment with chemotherapy is not curative and causes considerable side effects. The combination of bexarotene and denileukin diftitox is associated with an acceptable safety profile and a likely synergistic effect because bexarotene is capable of modulating expression of IL-2 receptor and enhance the susceptibility of T-cell leukemia cells to denileukin diftitox. In the case reported here, the response to this combined treatment was satisfactory and well tolerated. The patient showed a complete regression of pruritus, restlessness, and insomnia. Skin lesions improved partially, and lymphadenopathy was reduced and finally disappeared completely.
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PMID:Advanced-stage primary cutaneous T-cell lymphoma treated with bexarotene and denileukin diftitox. 2193 72

IL-2, a cytokine with pleiotropic effects, is critical for immune cell activation and peripheral tolerance. Although the therapeutic potential of IL-2 has been previously suggested in autoimmune diseases, the mechanisms whereby IL-2 mitigates autoimmunity and prevents organ damage remain unclear. Using an inducible recombinant adeno-associated virus vector, we investigated the effect of low systemic levels of IL-2 in lupus-prone MRL/Fas(lpr/lpr) (MRL/lpr) mice. Treatment of mice after the onset of disease with IL-2-recombinant adeno-associated virus resulted in reduced mononuclear cell infiltration and pathology of various tissues, including skin, lungs, and kidneys. In parallel, we noted a significant decrease of IL-17-producing CD3(+)CD4(-)CD8(-) double-negative T cells and an increase in CD4(+)CD25(+)Foxp3(+) immunoregulatory T cells (Treg) in the periphery. We also show that IL-2 can drive double-negative (DN) T cell death through an indirect mechanism. Notably, targeted delivery of IL-2 to CD122(+) cytotoxic lymphocytes effectively reduced the number of DN T cells and lymphadenopathy, whereas selective expansion of Treg by IL-2 had no effect on DN T cells. Collectively, our data suggest that administration of IL-2 to lupus-prone mice protects against end-organ damage and suppresses inflammation by dually limiting IL-17-producing DN T cells and expanding Treg.
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PMID:IL-2 protects lupus-prone mice from multiple end-organ damage by limiting CD4-CD8- IL-17-producing T cells. 2506 76


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