Lymphocyte subpopulations in primary immunodeficiency disorders.

Venous blood mononuclear cells from 42 children with primary immunodeficiency disorders and from controls matched for age were studied for lymphocyte subpopulations by E rosetting, surface immunoglobulin, and a panel of anti T cell monoclonal antibodies (OKT series). In 3 cases of severe combined immunodeficiency (SCID) due to adenosine deaminase deficiency, very few circulating T or B cells were found. The other 7 cases of SCID all had normal or, in 3 cases, very high numbers of circulating B cells, but in 6 of these very few cells showed T cell markers. One child had very high numbers of B cells and T cells with an immature pattern of reactivity similar to that found on common thymocytes. In T cell deficient children no consistent pattern was found, but in those with cartilage hair hypoplasia with immunodeficiency there was a low helper (OKT4) to suppressor (OKT8) ratio and high numbers of circulating OKT10 positive cells. In cases of X-linked agammaglobulinaemia circulating B cells were not found but the pattern of T cell markers was normal. In cases of common variable hypogammaglobulinaemia there was a wide scatter of helper (OKT4) to suppressor (OKT8) cell ratios. Five children were studied before and after treatment with the synthetic thymic hormone preparation TP5. There were appreciable alterations in the pattern of staining with anti T cell monoclonal antibodies in 4 of these cases, but in 1 case only was this accompanied by improvements in clinical and immune function.     

Long-term study on T lymphocyte subsets in newly diagnosed type 1 diabetes mellitus

T lymphocyte subsets in peripheral blood from 16 newly diagnosed type 1 diabetic children were studied prospectively at four time intervals: as soon as possible after diagnosis and 1, 4 and 12 months later. T lymphocyte subsets were analysed using monoclonal antibodies and counted by cytofluorimetry. The percentage of T lymphocytes (OKT3+ cells) did not change at the four study times. The percentage of helper/inducer T cells (OKT4+ cells) was high at the diagnosis (43.1 +/- 2.1%), but decreased after 1 and 4 months with no difference in the control values. The percentage of suppressor/cytotoxic T lymphocytes (OKT8+ cells) was low at the diagnosis, but increased after 1 and 4 months. The OKT4/OKT8 ratio was 2.31 +/- 0.22 at the diagnosis study, decreasing to 1.83 after 1 month, compared with 16 sex- and age-matched control children. The high percentage of helper/inducer T lymphocytes and low number of suppressor/cytotoxic T cells at onset of diabetes favour immune reactions that lead to beta-cell damage.     

Fatal aplastic anemia in a child with Down's syndrome

An infant with Down's syndrome developed severe persistent neutropenia at the age of 9 months and fluctuating anemia and thrombocytopenia at one year of age which terminated as full-blown aplastic anemia at 26 months of age. Immunological evaluation revealed increased peripheral and bone marrow lymphocytes and impaired blood OKT4: OKT8 ratio. Bone marrow granulocyte-macrophage colony forming cells (GM-CFC) were markedly increased, while peripheral blood mononuclear cells (PBMN) produced normal numbers of colonies. The patient's PBMN and serum were both somewhat inhibitory to normal bone marrow derived GM-CFC, suggesting the existence of a suppressor activity both in his serum and PBMN. This unusual course of aplastic anemia and the abnormalities in T-cells and hematopoiesis in Down's syndrome are discussed.     

Fatal Aplastic Anemia in a Child with Down's Syndrome

ABSTRACT. An infant with Down's syndrome developed severe persistent neutropenia at the age of 9 months and fluctuating anemia and thrombocytopenia at one year of age which terminated as full-blown aplastic anemia at 26 months of age. Immunological evaluation revealed increased peripheral and bone marrow lymphocytes and impaired blood OKT4: OKT8 ratio. Bone marrow granulocyte-macrophage colony forming cells (GM-CFC) were markedly increased, while peripheral blood mononuclear cells (PBMN) produced normal numbers of colonies. The patient's PBMN and serum were both somewhat inhibitory to normal bone marrow derived GM-CFC, suggesting the existence of a suppressor activity both in his serum and PBMN. This unusual course of aplastic anemia and the abnormalities in T-cells and hematopoiesis in Down's syndrome are discussed.     

Unusual Lack of the Epitope Recognized by OKT4 on the Helper/Inducer T Lymphocytes

Lack of the epitope recognized by OKT4 monoclonal antibody on the helper/inducer T lymphocytes in a 14-year-old boy with IgA nephritis is described. The lymphocytes reacted normally with OKT3 /Leu4 and OKT8/αLeu2a monoclonal antibodies but not with OKT4 monoclonal antibody. Studies with other monoclonal antibodies (αLeu3a, OKT4A, OKT4B, OKT4C, OKT4D) which also identify the helper/inducer T lymphocyte subset revealed that cells of this population were present in normal numbers among the lymphocytes of the peripheral blood. Staining with OKT4 plus αLeu3a in normal persons indicated that T4 antigen is present on a small population of lymphocytes which lack Leu3a antigen. Further, the intensity of staining of the majority of cells in the subpopulation is increased when these two fluorescienated antibodies are used together. In this patient neither this small OKT4⁺ Leu 3a^- population nor the cells bearing the Leu3a antigen showed OKT4 staining. The findings in the surface marker analysis of E+ OKT8- peripheral lymphocytes which were achieved by panning of the patient's peripheral cells indicated the existence of a population of E⁺OKT8^- peripheral lymphocytes which were achieved by panning of the patient's periphera cells indicated the existence of a population of E⁺ (4A⁺4B⁺4C4D⁺)αLeu3al⁺ ly mphocytes in this patient. Lymphocyte responses to PHA, ConA and PWM, however, were all within normal range. Further, this patient had normal serum immunoglobulin levels and exhibited no symptoms or signs of immunodeficiency. These findings indicate that the patient under study has functionally normal helper/inducer T lymphocytes which lack the epitope recognized by OKT4 monoclonal antibody.     

T cell subsets in human colostrum

Lymphocytes from 10 paired colostrum and peripheral blood specimens were examined to determine if the colostral T cell population differs from the peripheral blood T cell population in subset distribution. The percentages of lymphocytes staining with OKT3, OKT4, and OKT8 murine monoclonal antibody were determined. Lymphocytes from colostrum were 74.7 +/- 2.5% OKT3+, 50.6 +/- 2.3% OKT4+, 24.0 +/- 1.7% OKT8+, whereas peripheral blood lymphocytes were 78.7 +/- 1.9% OKT3+, 48.4 +/- 1.4% OKT4+, and 29.8 +/- 1.6% OKT8+. The percentage of colostrum lymphocytes positive for OKT3 was significantly although not strikingly lower than the OKT3 percentage for blood lymphocytes (p less than 0.05). This difference was due to the lower percentage of OKT8 positive lymphocytes in colostrum compared with blood (p less than 0.01). Although the T cell subset distribution of colostrum generally appears to be similar to that in the peripheral blood, there were small differences in OKT3 and OKT8 percentages that were statistically significant suggesting the possibility of some selectivity of the colostral T cell population.     

小儿特发性血小板减少性紫癜血小板相关抗体、T细胞亚群检测及其临床意义

本文对1989年9月至1995年2月收治的112例小儿特发性血小板减少性紫癜的血小板相关性抗体、T细胞亚群检测及其临床意义进行了探讨。结果表明：急、慢型无论是OKT3及OKT4+均低于正常对照组，且有显著性差异，P值均＜0．05；而OKT8+与正常对照组相比则较高，P值＜0．025。但是，急、慢两型相比均未见统计学上显差性差异。本文的检测血小板抗体lgG、IgM及IgA，显示均有所增高尤以PAIgG最明显，阳性率达85．7％，与文献报道近似。经治疗10例血小板动态变化，PAIg随着血小板的恢复均下降至正常，呈负相关.     

Abnormal serum IgG subclass pattern in children with Down's syndrome.

Susceptibility to infections is a well known feature of Down's syndrome. The possible relation between this predisposition and the serum concentrations of the IgG subclasses was studied in 38 children with Down's syndrome aged 1-12 years. An age matched group of 50 healthy children served as controls. The serum concentrations of IgG1 and IgG3 were significantly raised among children with Down's syndrome in all three age groups studied (that is 1-2.5, 4-8, and 9-12 years). The serum concentrations of IgG2 were normal in the first two groups but significantly reduced in the third age group. In contrast, the concentrations of IgG4 among children with Down's syndrome were significantly reduced in all three age groups. Moreover, among the children with Down's syndrome aged 4-12 years 68% (15/22) had IgG4 concentrations below 2 SDs of the geometrical mean of the controls. The results may partially explain the proneness of children with Down's syndrome to infections with encapsulated bacteria. Although the underlying cause of these abnormalities is unknown, IgG subclass determination seems relevant in the clinical evaluation of children with Down's syndrome.     

Varicella arthritis. Report of a case

A rare case of varicella with bilateral acute arthritis of the knee is described. Clinical features and laboratory results of the patient are briefly compared with those of other sixteen cases previously published. The study of immune response shows a decrease of helper T cells (OKT4+) and an increase of suppressor/cytotoxic T cells (OKT8+) with a normal response of lymphocytes to PHA.     

The measurement of leukocyte subsets in the peripheral blood of cancer patients with solid tumors using monoclonal antibody reagents

Monocyte and lymphocyte subsets were quantitated in the peripheral blood of normal subjects and patients with solid tumors using the monoclonal antibody reagents OKM1, BRL63D3, OKT3, OKT4, and OKT8. Percentages and numbers of cells reacting with monoclonal reagents were analyzed by indirect immunofluorescence. Correlations between leukocyte subset values and stage of disease or immunocompetence were sought. No differences from normal were seen in the percentage of OKT3, OKT4, and OKT8 cells or in the ratios of OKT4/OKT8 cells in peripheral blood mononuclear cells (PBMC) from all cancer patients, patients with localized disease, or patients with advanced disease. A significant decrease in absolute numbers of lymphocytes, OKT3 cells, OKT4 cells, and OKT8 cells was seen in the peripheral blood of patients with advanced disease reflecting the absolute lymphopenia of these patients. A significant increase was seen in the percentages of PBMC reacting with OKM1 and BRL63D3 from patients with advanced disease compared with normal donors or localized disease patients. A positive correlation was found between PHA responsiveness and absolute numbers of OKT3 and OKT4 cells. A negative correlation was found between PHA responsiveness and percentages of OKM1 cells. These data indicate that malignant disease does not alter T cell subset percentages in patient peripheral blood but may decrease their absolute numbers in association with absolute lymphopenia. On the other hand, percentages of OKM1 and BRL63D3 cells are increased in patients with advanced solid tumors in association with impaired PHA responsiveness.     

The human cytolytic T lymphocyte response to transplantation antigens

Cytolytic T lymphocytes are important effectors in the immune response to allografts, viral infections, and some tumors. Cytolytic T lymphocyte lines and clones have been generated and used to define functionally relevant effector and target cell surface molecules. The major target antigens of the human allogeneic response are the major histocompatibility complex antigens. Functionally relevant effector antigens include LFA-1, LFA-2, LFA-3, OKT4, OKT8, OKT3, and Ti, the T cell receptor. The diagnostic and therapeutic implications of T cell surface molecules are discussed.     

Antibody deficiency without decrease in the level of serum immunoglobulins

The paper reports the case of a 14 year-old boy, born at full term with intra-uterine growth retardation (1,640 g) who presented with short stature, generalized eczema and recurrent infections. During the first years of life, hypogammaglobulinemia with antibody deficiency occurred. The in vitro T lymphocyte function was normal. The infections have become less severe. The plasma levels of IgA, IgG, IgM and IgE are normal. There is hyperimmunoglobulinemia D. The deficiency of antibodies against most of the tested antigens persists. T and B lymphocyte counts are normal. The in vitro lymphocyte proliferation with Concanavalin A, Phytohemagglutinin, Pokeweed mitogen and Nocardia is normal. The OKT4+ and OKT8+ cell counts are normal. The ratio "helper T cell/suppressive T cell activity" appears to be abnormal. A very prolonged maturation delay, possibly associated with fetal hypotrophy may be hypothesized.     

Childhood common variable immunodeficiency with autoimmune disease

Clinical and laboratory findings in eight patients with childhood common variable immunodeficiency and autoimmune disease are described. Six of the eight patients had initial signs of the disease, persistent secretory diarrhea, recurrent upper respiratory tract infections, or both, in the first year of life. Autoimmune manifestations included idiopathic thrombocytopenia (4/8), hemolytic anemia (3/8), secretory diarrhea (4/8), arthritis (2/8), chronic active hepatitis (2/8), parotitis (2/8), and Guillain-Barré syndrome (2/8). In addition to the expected sinusitis, otitis, and pneumonia caused by encapsulated bacteria, these patients also had severe infections with viruses of the herpes group. Most of these patients had lymphadenopathy, splenomegaly, growth failure, and failure to develop secondary sexual characteristics. Laboratory studies demonstrated a significant increase in the ratio of T cells expressing the T helper phenotype (OKT4) to T cells expressing the T suppressor-cytotoxic phenotype (OKT8) (T4/T8). This increase could be attributed to a decrease in the absolute number of T8 cells. Additional findings included fluctuating levels of serum immunoglobulins and markedly diminished in vitro antibody production by B cells. The clinical course was relapsing and remitting, and dominated by the autoimmune manifestations of the disease. This group of patients constitutes a distinct subset of children with hypogammaglobulinemia, a subset with a complex, multisystemic disorder associated with significant morbidity and mortality.     

Thyroid function in children with Down's syndrome]

The aim of the present study was to evaluate thyroid function in 45 Down's syndrome patients in order to verify the hypothesis of an increased risk of thyroid disorders associated with trisomy 21. A patient with subclinical hypothyroidism (TSH 16.6 microU/ml; T4 6.4 micrograms/dl) was diagnosed in a group of 28 subjects with Down's syndrome studied at a mean age of 6 years and 5 months using T3, T4, FT3, FT4, TSH assays and clinical examination. T4 and TSH values were also measured in 10 of these children at the neonatal screening. One infant presented transient neonatal hyperthyrotropinemia but later became euthyroid. The analysis of thyroid hormone values at the neonatal screening of other 17 subjects with Down's syndrome did not reveal other cases with thyroid function disorders. The results of this study highlight that altered thyroid functions are evident in children with trisomy 21 associated with heart anomalies. A careful clinico-endocrinological follow-up of patients with Down's syndrome is recommended in order to ensure an early diagnosis of thyroid function disorders and/or autoimmune diseases which might complicate the evolution of trisomy and negatively affect outcome.     

In vitro effect of a bovine thymic extract (thymostimulin) on T-cell differentiation in cord blood lymphocytes

Cord blood lymphocytes were isolated from 40 normal newborns. The initial 20 samples were used to determine the dose-response curve of bovine thymic extract (Thymostimulin) by the measurement of active T cells. Results showed that the active T cells increased significantly when the Thymostimulin concentration was increased to 50 ng/ml and 100 ng/ml. The remaining 20 samples were divided into three portions and preincubated either with 50 ng and 100 ng of Thymostimulin or without Thymostimulin. The total T cells, active T cells, B cells, T-cell subsets, and lymphoproliferative responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen were determined. The results showed that the active T cells, total T cells, B cells, OKT4 cells, and OKT8 cells were significantly increased after Thymostimulin treatment. The lymphoproliferative responses were also significantly increased. These data strongly support our conclusion that Thymostimulin has a marked stimulating effect on human lymphocyte proliferation and differentiation.     

Thyroid dysfunction in children with Down's syndrome

Thyroid function tests were carried out on 320 children with Down's syndrome aged between 5 d and 10 y. Thyroid function was normal in 230 patients (71.9%) and abnormal in 90 (28.1%). Six patients (1.8%) had primary congenital hypothyroidism, one patient had acquired hypothyroidism and two had transient hyperthyrotropinaemia of the newborn. Sixteen of the remaining 81 patients (25.3%) had compensated hypothyroidism with increased thyroid-stimulating hormone (TSH) levels (11-20 mU l -1 ). Their T 4 levels were found to be either normal or close to the lower limit of normal. These cases were started on thyroxine therapy. Sixty-five of the 81 patients had a mild compensated hypothyroidism with mild TSH elevation (6-10 mU l -1 ). None of the patients had hyperthyroidism. The antithyroid antibodies were positive in the acquired hypothyroidism case.

Conclusion: The prevalence of congenital hypothyroidism was 1.8% in children with Down's syndrome while 25.3% of them had compensated hypothyroidism. It is suggested that Down's syndrome patients with normal thyroid functions and those with compensated hypothyroidism should be followed annually and every 3 mo, respectively. Besides congenital hypothyroidism cases, those with TSH levels between 11 and 20 mU l -1 may benefit from treatment with low-dose thyroxine.     

T cell subsets in glomerulonephritis

Abnormal lymphocyte function has been postulated to have a pathogenetic role in nephrotic syndrome. In an attempt to investigate the pathogenetic role of lymphocyte subsets in human glomerular disease, we studied 110 children suffering from nephritis during the acute nephrotic phase or nephritis without steroid treatment, 4 weeks later after steroid treatment, in remission and relapse. These patients included minimal change nephrotic syndrome (MCNS) 15 cases, focal segmental glomerular sclerosis (FGS) 6 cases, mesangial cell proliferative nephropathy (MesPGN) 42 cases, membranoproliferative glomerulonephritis (MPGN) 2 cases, hepatitis B surface antigenemia associated with membranous nephropathy (HBVMN) 10 cases, IgA mesangial nephropathy (IgAN) without nephrotic syndrome 7 cases, poststreptococcal glomerulonephritis (PSGN) 24 cases and chronic glomerulonephritis (CGN) 4 cases. There was no significant difference in the total lymphocyte count of each different pathological group of nephritis except that lymphopenia was noted in the CGN patients. When the lymphocyte phenotypic profile was examined, OKT8 cells were significantly increased in the MesPGN patients and both OKT4 and OKT8 cells were significantly increased in HBVMN. Comparison of MCNS and MesPGN during the acute nephrotic phase showed the OKT4/OKT8 ratio decreased significantly in MesPGN. Four weeks after steroid treatment, OKT4 cells decreased both in MCNS and MesPGN being pronounced in MCNS. In the remission stage with steroid treatment the OKT4/OKT8 ratio decreased in MCNS and was mildly elevated in MesPGN. In relapse, the OKT4/OKT8 ratio was the same as it was during the onset of nephrotic phase. MCNS cases were steroid responsive whereas in MesPGN there were frequent relapses or partial steroid response.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transient remission after intercurrent measles infection in a patient with hyperimmunoglobulin E syndrome

A 5-yr-old patient with hyper IgE syndrome contracted measles. This was accompanied by a temporary disappearance of his skin lesions. The patient had a long history of recurrent infections, chronic eczematoid pruritic dermatitis, and elevation of serum IgE level since infancy. Immunologic studies revealed decreased suppressor T cells (OKT8 cells) with increased IKT4/OKT8 ratio, defect in suppressor T cell function, and decreased chemotactic index. In February 1985, when he developed an interrcurrent measles infection at age of 5, the eczematoid pruritic dermatitis disappeared completely and immunologic defects improved transiently, with normalization of OKT4/OKT8 ratio, decrease in in vitro IgE synthesis, in vivo serum IgE level, and interleukin-2 production, decreases in IgG Fc receptor-bearing cells and autologous mixed lymphocyte reaction, and normalization of chemotactic index. One month later, the eczematoid skin lesion relapsed and immunologic defects reappeared. These studies suggested that the pathogenesis of hyper IgE syndrome involved a hypofunction of suppressor T cell. The transient remission associated with measles infection is probably related to the effect of the virus on the helper T cells, resulting in a normalization of OKT4/OKT8 ratio and IgE production.     

An uncommon cause of seizures in children living in developed countries: neurocysticercosis -a case report

Background

It is well known that certain non-thyroidal critical illness may lead to euthyroid sick syndrome(ESS). There are little reports about the change of thyroid hormone in the children's central nervous system (CNS) infections.

Results

The results of serum TT3, TT4 and TSH in these children were compared with those in 20 cases of healthy adults and 20 cases of adults with primary hypothyroidism. Serum T3 and T4 were decreased in 34/78 children with CNS infections, T3 and T4 were much lower than those of healthy adult (p < 0.05), but still higher than that of the primary hypothyroidism (p < 0.05), and TSH levels were not significant differences among children with CNS infections and children with non-CNS infections (p > 0.05). Low T3 and T4 levels in serum and cerebrospinal fluid(CSF)were predominant in children with serious infections of CNS, 31/34 (percent 91.17) cases of serious CNS infection had low serum TT3 and/or TT4. The low T3 with low T4 was seen in 14/34 children of severe CNS infections, 3 of them died. The levels of CSF T3 (X ± SD = 0.39 ± 0.47 ng/ml) and T4 (x ± SD = 1.02 ± 1.27 ug/dl) in the serious CNS infections were lower than that of non-CNS infections T3 (x ± SD = 0.93 ± 1.23 ng/ml), and T4 (x ± SD = 2.42 ± 1.70 ug/dl), 7 died children were all in the subjects of low T3 and/or low T4. In 22 children with non-CNS infections, serum T3 and T4 levels were lower than that of healthy adult, but have not significant difference(p > 0.05).

Conclusions

These results suggest that detection of TT3, TT4 and TSH in serum and/or CSF simultaneous or alone in analyses would be valuable in correctly judging thyroid function and evaluating the prognosis of the children with infections of CNS. Measuring a little amount of blood (1 ml)or CSF required for this method is a simple, convenient and accurate method.     

Immunological evaluation of 60 children with AIDS

OBJECTIVE: The immunologic defects that occur in children with HIV infection are important tests to both diagnosis and therapeutic response. The objective of this study was to verify the immunologic abnormalities in 60 children with AIDS, in Florianópolis, Santa Catarina State, Brazil. METHODS: Serum immunoglobulin levels were determined by nephelometry and compared to a normal pattern for Brazilian children. The lymphocyte T helper (CD4+) and the lymphocyte T suppressor (CD8+) count and percentage, and the ratio between them, determined by commercial flow cytometry, were compared to a pattern for healthy children of HIV-positive mothers. RESULTS: The mean serum IgG levels was higher in the children with AIDS (p<0.005). The mean serum IgM levels was higher in the children with AIDS in the age group between 13 and 108 months (p<0.005). The CD4+ lymphocytes count was below the inferior limit of the 95% confidence interval of the median reference values to each group of age in 50 (84.7%) of the 59 determinations. The CD4+ lymphocytes percentage was much lower than the percentages of reference. The graph curve of the medians of the ratio between lymphocytes CD4+ and CD8+ to each group of age was below the fifth percentile of the graph curve of the medians of reference. CONCLUSIONS: The hypergamaglobulinemia and the lymphocyte T CD4+ count and percentage are sensitive indicators of HIV infection, observed in the present study. Immunologic evaluation of the HIV-positive children is recommended, including those younger than 18 months of age.