Disease relevance of Lymphopenia

• In most instances, marked deficiency of the purine catabolic enzyme adenosine deaminase results in lymphopenia and severe combined immunodeficiency disease [1].
• CD4 lymphocytopenia without HIV in patient with cryptococcal infection [2].
• Opportunistic infections and CD4 lymphocytopenia with interferon treatment in HIV-1 infected patients [3].
• CONCLUSIONS: The presence of both a relative lymphocytopenia and an elevated rapid creatine kinase-MB level was an accurate early marker of myocardial infarction that appeared to improve the sensitivity of early diagnosis compared with that of ST-segment elevation alone [4].
• Targeted disruption of Bcl-2 alpha beta in mice: occurrence of gray hair, polycystic kidney disease, and lymphocytopenia [5].

Psychiatry related information on Lymphopenia

• Nutritional status, ACTH, or plasma cortisol in dementia cohort were also not explanatory of their lymphopenia [6].
• Colonization was significantly more frequent in IV drug users, CDC groups IV, and in subjects with lymphocytopenia, CD4+ cell depletion, or elevated beta-2 microglobulin [7].

High impact information on Lymphopenia

• SIRT6-deficient mice are small and at 2-3 weeks of age develop abnormalities that include profound lymphopenia, loss of subcutaneous fat, lordokyphosis, and severe metabolic defects, eventually dying at about 4 weeks [8].
• Here we describe five patients with growth retardation, microcephaly, and immunodeficiency characterized by a profound T+B lymphocytopenia [9].
• Lymphopenia developed in 32 of 56 patients treated with 2 mg of azathioprine per kilogram per day for more than two years [10].
• Mouse studies showed that IL-2 therapy induced expansion of existent T(reg) cells in normal hosts, and IL-2-induced T(reg) cell expansion was further augmented by lymphopenia [11].
• DOCK2-deficient mice (DOCK2-/-) exhibited migration defects of T and B lymphocytes, but not of monocytes, in response to chemokines, resulting in several abnormalities including T lymphocytopenia, atrophy of lymphoid follicles and loss of marginal-zone B cells [12].

Chemical compound and disease context of Lymphopenia

• Genetic deficiencies in the purine catabolic enzyme adenosine deaminase (ADA) in humans results primarily in a severe lymphopenia and immunodeficiency that can lead to the death of affected individuals early in life [13].
• Additionally, ipriflavone induces lymphocytopenia in a significant number of women [14].
• Deoxyadenosine has been implicated as the toxic metabolite causing profound lymphopenia in immunodeficient children with a genetic deficiency of adenosine deaminase (ADA), and in adults treated with the potent ADA inhibitor deoxycoformycin [15].
• These elevated concentrations of adenosine, deoxyadenosine, and dATP are similar to those we observed in another older adenosine deaminase-deficient patient and may explain the impaired immune function and lymphopenia seen at birth [16].
• These results indicate that neurogenic stimuli from the surgical area, probably through their influence on adrenal hormones (cortisol and adrenaline), are the main mediators of postoperative lymphopenia and are partly responsible for postoperative granulocytosis [17].
• The presence of lymphopenia at diagnosis and at baseline and higher levels of serum creatinine and C-reactive protein at baseline were positively associated with progression of carotid IMT (P=0.006, P=0.043, P=0.037, and P=0.049, respectively) [18].
• Inhibition of tumor Gal-1 with either shRNA or thiodigalactoside ablated radiotherapy-induced lymphopenia [19].

Biological context of Lymphopenia

• Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells [11].
• However, T(S) cells were not impaired in their proliferative response to lymphopenia, which was dependent on major histocompatibility complex class II expression [20].
• Instead, ontogenic relationships, steady-state labeling kinetics, and adoptive transfer experiments suggest that CD21/35(high) CD23(+) splenocytes serve primarily as precursors for MZ B cells, although their developmental potential seems to be broader and is influenced by environmental cues that are associated with lymphopenia [21].
• A high level of apoptosis associated with thymic atrophy and peripheral blood (PB) lymphopenia was also evident in N-ras reconstituted mice [22].
• In contrast, the increase in CD4 cell counts was less in patients treated with hydroxyurea because of lymphopenia, and adverse events were more frequent in hydroxyurea-treated patients [23].

Anatomical context of Lymphopenia

• IgG cell-associating antilymphocyte antibodies present in SLE sera may cause T cell disturbances in vivo and may be related to the lymphocytopenia present in SLE patients [24].
• Four hundred milligrams of intravenous hydrocortisone administered 24 hr after infusion of labeled cells caused a profound but transient lymphocytopenia which was maximal at 4 hr with return of lymphocyte counts to normal by 24 hr after injection [25].
• Neutrophilia and lymphopenia were not affected by anti-TNF, whereas neutrophil degranulation, as measured by the plasma concentrations of elastase-alpha 1-antitrypsin complexes, was only slightly reduced (peak levels after endotoxin alone 31.0 +/- 3.4 ng/mL, versus 25.5 +/- 3.4 ng/mL after endotoxin with anti-TNF; P < .05) [26].
• Conversely, Hoxa9(-/-) mice displayed marked lymphopenia and substantial reductions of common lymphoid progenitors (CLPs) and lymphoid precursors, in addition to significant reductions of common myeloid progenitors (CMPs) and granulocyte/monocyte progenitors (GMPs) [27].
• Despite high IL-18 elevation, in vitro NK-cell cytotoxicity was severely impaired in HPS patients, in part due to NK-cell lymphopenia that was observed in a majority of patients but also secondary to an intrinsic NK-cell functional deficiency [28].

Gene context of Lymphopenia

• Moreover, whereas loss of the BH3-only protein Bim rescued mice lacking the prosurvival protein Bcl-2 from fatal polycystic kidney disease and lymphopenia, loss of Bik did not [29].
• In studying the immunologic consequences of TERC mutations, severe B lymphopenia and decreased immunoglobulin M (IgM) levels were noted [30].
• Arachidonic acid metabolites are implicated as biochemical intermediates in the production of the neutrophilia but not lymphopenia, since indomethacin and dexamethasone both completely abrogated IL-1-induced neutrophilia but did not affect the IL-1-induced lymphopenia [31].
• Functional and genetic data support the hypothesis that the gene responsible for the lymphopenia, Lyp, is also a diabetes susceptibility gene, named Iddm1 [32].
• The immunosuppressant FTY720 was phosphorylated and elicited lymphopenia in the Sphk1 null mice showing that SPHK1 is not required for the functional activation of this sphingosine analogue prodrug [33].

Analytical, diagnostic and therapeutic context of Lymphopenia

• Macrophage colony-stimulating factor (recombinant human M-CSF) given as a single intravenous injection to Lewis rats induces a dose-dependent peripheral monocytosis, neutrophilia, and lymphopenia [34].
• Splenic and peripheral blood flow cytometry studies of long-term hCTLA4-Ig-injected survivors showed a significant peripheral B-cell and CD4+ T-cell lymphopenia, consistent with GVHD [35].
• It has been reported that expression of RT6.2 in animal models may correlate with lymphopenia and genetically-induced insulin-dependent diabetes mellitus [36].
• Adrenalectomy did not alter the IL-1- or rTNF-induced neutrophilia or lymphopenia, also demonstrating that neither monokine mediates its hematologic effects on peripheral blood leukocytes via the release of adrenal hormones.(ABSTRACT TRUNCATED AT 400 WORDS)[31]
• Risk factors for CD4 lymphopenia in patients treated with a tenofovir/didanosine high dose-containing highly active antiretroviral therapy regimen [37].

References