Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the peripheral blood of patients with Crohn's disease (CD) the numerical distribution of the three major B lymphocyte subsets was determined by the identification of surface immunoglobulins using F(ab)(2)-antibody fragments. T cell counts were also obtained and the number of null cells was calculated. Twenty-eight patients with Crohn's disease including 14 patients with previously untreated and very short-standing disease (group CD 1) and 14 patients with long-standing and/or previous drug treated disease (group CD 2) were compared with 28 sex and age-matched normals as well as with 13 patients with acute inflammatory bowel disease (group D). Patients in group D and inactive patients of group CD 1 showed a significant absolute lymphocytosis due to an increase in both the three B cell subsets and the T cells, without changes in the null cells. While the proportion of T cells was normal, there was a significant relative B lymphocytosis and a relative null cytopenia in these patients. Active CD 1 patients, however, showed significantly lower absolute lymphocyte and T cell numbers. In group CD 2, there was a significant absolute lymphopenia caused by an equal decrease in B and T cells. Highly active CD 2 patients showed higher absolute null cell counts than inactive patients. With increasing disease duration there was a significant decrease of the relative and absolute B cell concentrations. The data obtained suggest that T and B cell populations in the peripheral blood are reduced in certain patients with Crohn's disease and that this occurs secondarily to activity of disease, chronicity of disease, and the effects of therapy.
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PMID:Immune status in Crohn's disease. 3. Peripheral blood B lymphocytes, enumerated by means of F(ab)2-antibody fragments, Null and T lymphocytes. 31 53

Cellular immunological abnormalities were studied in a patient with protein-losing enteropathy associated with constrictive pericarditis. Analysis of lymphocyte subpopulations in peripheral blood showed lymphopenia with a decrease of CD3+ and CD4+ T cells, whereas CD8+ lymphocytes, B cells and NK cells were within the normal range. Fecal loss of lymphocytes as a cause of lymphopenia was evidenced by a marked excretion of 111-indium-labeled peripheral blood mononuclear cells via stool. Proliferative responses against several mitogens were severely reduced as was in vitro IgG production. Delayed-type hypersensitivity reaction against a variety of antigens was absent. Vaccination with tick-borne encephalitis virus, used for primary immunization, and with the recall antigen tetanus toxoid resulted in a blunted antibody response. After pericardectomy, the severity of enteric protein loss declined, serum immunoglobulin levels returned to the normal range, and total lymphocytes and CD3+ and CD4+ counts increased but remained low even 12 months after surgery. Fecal loss of lymphocytes was found to be reduced after pericardectomy, but was higher than that seen in a disease control patient with active inflammatory bowel disease. In vitro immunoglobulin production returned to normal, DTH could be demonstrated against purified protein derivative and proteus antigen, but mitogen-driven blastogenic response of lymphocytes remained low. Revaccination with tick-borne encephalitis and tetanus toxoid antigens seven months after surgery resulted in a dramatic increase of serum levels of antibodies against both antigens, comparable to that seen in healthy control individuals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cellular immunodeficiency in protein-losing enteropathy. Predominant reduction of CD3+ and CD4+ lymphocytes. 167 Jun 32

From 1980-1986 intestinal mucosal lymphangiectasia was diagnosed histologically in eight patients (6 weeks to 16 years; four males/four females; seven white). The presenting features were diarrhea (six/eight), vomiting (four/eight), and growth deficit (seven/eight). Additional conditions in these patients included asthma, urinary tract infection, esophageal atresia, hydrops fetalis, inflammatory bowel disease, malabsorption syndrome, and thymic hypoplasia. Hypoalbuminemia and edema (four/eight) were more prominent in those patients under 5 years of age. Two had systemic lymphangiectasia and lymphopenia. The patients responded variably to hyperalimentation and dietary supplements, depending on the extent of their lymphangiectasia and the age at onset of symptoms. Dilated lymphatics were seen in the small intestinal mucosa under the surface epithelium. Lesions were often focal, requiring several biopsies or serial sections for detection. Other common findings were mild to moderate lymphoplasmacytic inflammation and mild to moderate villous injury with blunting and edema. Mild inflammation without lymphangiectasia was also present in esophageal, gastric, or colonic biopsies. Diagnosis should be made on the basis of endoscopic findings or in small-intestinal inflammatory conditions even in the absence of a classic clinical picture. Histologic confirmation may require more than one serially sectioned biopsy. This study confirms the diversity of disorders that may be associated with intestinal lymphangiectasia and shows that the disease in infants is more severe and generalized.
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PMID:Intestinal lymphangiectasia in children: a study of upper gastrointestinal endoscopic biopsies. 274 90

The diagnosis of protein-losing enteropathy (PLE) should be considered in all patients with hypoalbuminemia and edema without other known causes, and established by plasma alpha(1)-antitrypsin (alpha(1)-AT) clearance or nuclear studies. The therapy for PLE should focus principally on the treatment of the underlying disease after it has been identified. Therapeutic goals should include improvement of hypoalbuminemia, edema, and lymphopenia. The existing primary literature for therapy of PLE syndromes consists mainly of case reports and expert opinions, subject to substantial reporting bias and unknown rates of spontaneous remission; the rarity of and the diversity among this set of diseases make future large randomized trials unlikely. Therapeutic choices, therefore, must involve clinical acumen, empiricism, and understanding of the pathophysiology of the underlying disease process, and must be tailored to each individual patient's syndrome. Dietary interventions including hypolipidic, high-protein regimens, supplemented by medium-chain triglycerides (MCTs), are extremely useful, particularly in protein loss due to increased lymphatic pressure. Corticosteroids can be very useful in certain cases of PLE (though not without substantial long-term toxicity) when clinical serologic or histologic markers of inflammatory disease are present. Octreotide is a well tolerated drug that has been demonstrated to improve PLE in some patients, and is worth consideration. Octreotide is a well tolerated drug that has been demonstrated to improve PLE in some patients, and is worth consideration. Surgery finds its best role in treating gastrointestinal protein loss from neoplasia, inflammatory bowel disease, and hypertrophic gastritis. Most other PLEs are distributed too widely for surgical intervention. Protein-losing gastropathy (PLG) behaves somewhat differently from the general group of PLE, marked by excellent responses to elimination of Helicobacter pylori, antisecretory therapy, and surgical resection. Protein-losing enteropathy stemming from cardiovascular disease is best treated by medical or surgical cardiovascular interventions; however, some patients may respond to mucosa-directed therapy.
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PMID:Protein-Losing Enteropathy and Gastropathy. 1117 80

The CD4(+) T cell-mediated inflammatory response to Pneumocystis carinii (PC) critically contributes to the clinical severity of PC pneumonia. It has been suggested that lymphopenic conditions predispose individuals to this immunopathology, although the mechanisms remain poorly understood. Another set of evidence indicates that a subpopulation of CD4(+) T cells constitutively expressing the CD25 molecule prevent lymphopenia-induced autoimmunity and inflammatory bowel disease. We tested the ability of this CD25(+)CD4(+) population to regulate CD4(+) T cell-mediated inflammatory response to PC. Adoptive transfer of CD25(-)CD4(+) cells into PC-infected recombination-activating gene-2-deficient mice led to lethal pneumonia within 13 days post-transfer. PC infection appeared to trigger CD25(-)CD4(+) cells, since recipients with reduced PC load survived up to 5 weeks after transfer. In contrast, transfer of CD25(+)CD4(+) cells did not induce lethal pneumonia and prevented the development of the disease induced by CD25(-)CD4(+) cells. Furthermore, CD25(-)CD4(+) cells reduced the PC load in the lung, while CD25(+)CD4(+) cells suppressed this immune response. Our results indicate an essential role for CD25(+)CD4(+) T cells in the control of PC-driven immunopathology, and suggest that in immunocompromised hosts PC pneumonia may result from a deficiency in regulatory T cells.
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PMID:CD25+CD4+ regulatory T cells suppress CD4+ T cell-mediated pulmonary hyperinflammation driven by Pneumocystis carinii in immunodeficient mice. 1198 15

Mice lacking interleukin-7 (IL-7-/- mice) have no signs of autoimmune disease, contrary to other models of lymphopenia. We investigated whether the absence of disease was due to the fact that IL-7 is dispensable for the ontogeny, function, and homeostasis of regulatory CD4+ T cells. We show here that the establishment of the peripheral pool of Foxp3-expressing regulatory cells is IL-7 independent, and the premature involution of the thymus in IL-7-/- mice does not change the representation of the CD4+CD25+ T-cell compartment. In addition, CD4+CD25+ T cells expand in the absence of IL-7, without losing Foxp3 expression. The frequency of activated peripheral CD4+ T cells increases with age in both the CD25- and CD25+ compartments, with the CD4+CD25+ T cells displaying signs of constant activation. IL-7-/- CD4+CD25+ T cells control inflammatory bowel disease induced by IL-7-/- T cells even in hosts lacking IL-7. Depletion of the CD25+ T-cell subset after thymic involution results in a mild form of inflammatory bowel disease (IBD), which resolves concomitantly with the regeneration of this subset. This study shows for the first time that IL-7-/- mice have a robust regulatory Foxp3-expressing CD4+ T-cell compartment that controls T-cell-mediated disease. It also highlights the potential of the regulatory Foxp3-expressing CD4+CD25- T-cell population to restore a functional CD4+CD25+ T-cell compartment through an IL-7-independent pathway.
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PMID:Ontogeny, function, and peripheral homeostasis of regulatory T cells in the absence of interleukin-7. 1676 7

A 5-year-old Shetland Sheepdog was presented with a history of weakness, ataxia, anemia, thrombocytopenia, and occasional seizures. The dog had been treated for 6 months with prednisone for inflammatory bowel disease. A positive titer for Ehrlichia canis was detected 6 months before referral. The initial physical examination revealed a weak, laterally recumbent dog with pale mucous membranes. Neurologic examination revealed multiple neurologic deficits. A complete blood cell count (CBC) revealed normochromic, normocytic, nonregenerative anemia; lymphopenia; thrombocytopenia; and neutrophilic and monocytic leukocytosis. Urinalysis revealed proteinuria, with a specific gravity of 1.045. The dog was unresponsive to treatment and died. At necropsy, there was severe serofibrinous peritonitis and pleuritis, with randomly scattered dark brown necrotic foci present in multiple organs, including liver, spleen, kidney, and pancreatic lymph node. Histologically, there were extensive regions of parenchymal necrosis surrounded by neutrophils admixed with epithelioid macrophages, lymphocytes, and pigmented fungal organisms. Numerous brown, 2 to 6 microm in diameter, septate, branching hyphae, subsequently identified as Ochroconis gallopavum (formerly Dactylaria constricta var. gallopava), were observed.
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PMID:Fatal systemic phaeohyphomycosis caused by Ochroconis gallopavum in a dog (Canis familaris). 1709 56

We have analysed data from 150 patients initially classified as having CVID. About 10% had laboratory abnormalities suggesting known single gene disorders (eg: hyper-IgM syndrome), and in a few a genetic defect has been confirmed. We have attempted to sub-classify the remaining patients by analysis of their circulating lymphocytes. B lymphocyte markers have been used to estimate the numbers of circulating immature and class switched B cells; there is an association between the presence of high relative numbers of immature circulating B cells, splenomegaly and autoimmune disease. About 25% of CVID patients have a moderate CD4+ T lymphopenia, sometimes with a relative expansion of CD8+ T cells. About 30% of CVID patients have persistent relatively high levels of circulating CD8+ T cells binding immunogenic peptides from EBV or CMV. Many of these patients also have high relative numbers of circulating CD8+ perforin positive T cells, and there is evidence that these cells may be responsible for neutropenia or inflammatory bowel disease in some patients. The clinical spectrum of CVID is diverse, with some patients suffering from few infections, and over 50% have evidence of structural lung damage. About 25% of UK patients have chronic inflammation in various organs, particularly the lungs, liver and spleen, often with granulomatous changes. Steroids are used to treat many of the patients with chronic inflammatory complications, although trials are in progress with anti-TNF agents. The incidence of these inflammatory complications is different between countries, being rare in Sweden. Attempts to correlate clinical phenotypes with the laboratory abnormalities described above have been disappointing, suggesting that unknown genetic factors unrelated to the cause of the immunodeficiency determine the complications; attempts to identify some of these factors will be discussed. Finally a provisional scheme to sub classify CVID patients according to lymphocyte abnormalities will be presented, the purpose being to focus the screening of candidate genes causing CVID to specific subsets of patients.
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PMID:Clinical and Immunological Spectrum of Common Variable Immunodeficiency (CVID). 1730

Partial or total CD3 chain expression defects including CD3 gamma, epsilon, delta, and zeta chain are among the autosomally inherited SCID presenting with T-B+NK+ phenotype with lymphopenia. The clinical findings are generally severe in all except for CD3 gamma deficiency. Here we present a 10-month-old CD3 gamma deficient boy with IBD. The patient had suffered from intractable diarrhea, recurrent pulmonary infections and oral moniliasis since two months of age. Following the first allogeneic HSCT from his HLA-identical (6/6) sister after a reduced intensity regimen, a second transplantation was performed five months later. On day +19 after second transplantation, the CD3 TCR alpha/beta chain expression increased to 66% with development of full donor chimerism (98.6%). A significant improvement in diarrhea, perianal lesions, and rectal fistula was observed suggesting an improvement in inflammatory bowel disease. The patient died at home on day +50 with a sudden respiratory failure secondary to an undetermined infection. The case was interesting being the first reported case with SCID and inflammatory bowel disease who responded very well to HSCT by full recovery of intractable diarrhea, failure to thrive, laboratory findings, and improvement of fistula formation.
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PMID:Hematopoietic stem cell transplantation in a CD3 gamma-deficient infant with inflammatory bowel disease. 1848 19

Pathogenic lymphocytes in the enteric wall of inflammatory bowel disease patients display various abnormalities, including reduced sensitivity to apoptosis. We evaluated a therapeutic approach to elimination of cytotoxic cells, using two IL-2 fusion proteins, a diphtheria toxin (IL2-DT) and a caspase-3 (IL2-cas) conjugate. In models of acute (dextran sodium sulfate and trinitrobenzene sulfonic acid) and chronic (dextran sodium sulfate) toxic colitis, therapeutic doses of the fusion proteins improved survival and prevented colon shortening. While both chimeric proteins eradicated CD4(+)CD25(+)Foxp3(+) T cells in mesenteric LN, IL2-DT caused severe lymphopenia. In contrast, IL2-cas was equally protective and increased fractional expression of Foxp3. Similar effects of the fusion proteins were observed in healthy mice: IL2-DT caused lymphopenia and IL2-cas increased fractional expression of FoxP3. The fusion proteins induced apoptosis in CD25(+) T cells in vitro, with lower toxicity of IL2-cas to Foxp3(+) T cells. These data infer that targeted depletion of cells expressing the IL-2 receptor has therapeutic potential in models of inflammatory colitis, despite depletion of CD25(+) Treg. The IL2-cas fusion protein is particularly relevant to inflammatory bowel disease, as direct internalization of toxic moieties overcomes multiple pathways of resistance to apoptosis of colitogenic T cells.
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PMID:Targeted therapy to the IL-2R using diphtheria toxin and caspase-3 fusion proteins modulates Treg and ameliorates inflammatory colitis. 1973 74


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