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C Cunningham-Rundles

Publications and source records attributed to C Cunningham-Rundles.

At least 73 records · Page 4Linked to original sources
PubMed1988

In vitro induction of T cell-dependent B cell differentiation in patients with common varied immunodeficiency.

Patients with common varied immunodeficiency (CVI) are characterized by hypogammaglobulinemia. We investigated in vitro T cell-dependent B cell differentiation in CVI peripheral blood mononuclear cells by stimulating the T cells with an anti-CD3 (T3) monoclonal antibody. In cultures from CVI patients with no detectable circulating B cells, little immunoglobulin (Ig) was produced following anti-CD3 stimulation. In cultures from CVI patients with near-normal numbers of circulating B cells, anti-CD3 stimulation induced a normal percentage increase in Ig-secreting cells and appreciable (albeit subnormal) increases in IgG and IgM secretion. Cell-mixing experiments pointed to a quantitative, rather than qualitative, defect in B cell function in most of these CVI patients. Nevertheless, CVI T cells can induce substantial differentiation of autologous (and normal) B cells following anti-CD3 stimulation (which may mimic physiologic stimulation). This raises the possibility of correcting the hypogammaglobulinemia of CVI by in vivo or ex vivo administration of appropriate T cell stimuli.

Adolescent↗
PubMed1988

Chronic fatigue syndrome: a working case definition.

The chronic Epstein-Barr virus syndrome is a poorly defined symptom complex characterized primarily by chronic or recurrent debilitating fatigue and various combinations of other symptoms, including sore throat, lymph node pain and tenderness, headache, myalgia, and arthralgias. Although the syndrome has received recent attention, and has been diagnosed in many patients, the chronic Epstein-Barr virus syndrome has not been defined consistently. Despite the name of the syndrome, both the diagnostic value of Epstein-Barr virus serologic tests and the proposed causal relationship between Epstein-Barr virus infection and patients who have been diagnosed with the chronic Epstein-Barr virus syndrome remain doubtful. We propose a new name for the chronic Epstein-Barr virus syndrome--the chronic fatigue syndrome--that more accurately describes this symptom complex as a syndrome of unknown cause characterized primarily by chronic fatigue. We also present a working definition for the chronic fatigue syndrome designed to improve the comparability and reproducibility of clinical research and epidemiologic studies, and to provide a rational basis for evaluating patients who have chronic fatigue of undetermined cause.

Chronic Disease↗
PubMed1987

Immunoglobulin prophylaxis in patients with antibody deficiency syndromes and anti-IgA antibodies.

Sera from three hundred five patients with immunoglobulin deficiencies were analyzed for the presence of anti-IgA antibodies by using indirect agglutination and enzyme-linked immunosorbent assay (ELISA). Anti-IgA antibodies were observed in 15 of 68 (22%) patients with hypogammaglobulinemia and 53 of 185 (29%) patients with selective IgA deficiency, both groups having serum IgA less than 0.05 g/liter. The highest frequency, 6 of 10 or 60%, was noted for patients with a combined IgA-IgG2 deficiency. No anti-IgA antibodies were detected in 25 patients with serum IgA between 0.05 and 0.27 g/liter and normal amounts of serum IgM and IgG or in 17 patients with hypogammaglobulinemia who had serum IgA of 0.05-0.7 g/liter. The anti-IgA antibodies were primarily of the IgG class, but IgD and IgM anti-IgA were occasionally found. IgE anti-IgA antibodies could not be detected with the presently used technique. The IgG anti-IgA antibodies were mainly of the IgG1 subclass but occasionally also of the subclasses IgG2, IgG3, and IgG4. Of eight patients with anti-IgA antibodies, seven tolerated Ig prophylaxis with a commercial immunoglobulin preparation low in IgA when given either intramuscularly or intravenously. The titers of anti-IgA in the sera of these patients did not rise in relation to the prophylaxis. Only one of the eight patients had a history of previous anaphylactic reactions to IgA-containing blood products. He tolerated six Ig infusions during 5 months with the IgA-depleted preparation without any adverse effects but showed increasing levels of anti-IgA antibodies and ultimately experienced a near-fatal reaction at the seventh infusion.

Antibodies, Anti-Idiotypic↗
PubMed1987

Incidence of cancer in 98 patients with common varied immunodeficiency.

Ninety-eight patients with common varied immunodeficiency have been observed for periods of 1-13 years. In 1986, 78 were alive, 19 had died, and 1 could not be located. Eleven patients in the group had developed cancer; two patients had had two cancers. Of the total number of neoplastic malignancies, seven were non-Hodgkin's lymphoma, one patient had a Waldenstrom's macroglobulinemia, and nine of the patients who developed cancer were female. Cancer developed in the fifth or sixth decade of life for 10 of the 11 patients. These data show an 8- to 13-fold increase in cancer in general for patients who have this immunodeficiency and a 438-fold increase in lymphoma for females.

Agammaglobulinemia↗
PubMed1987

T-cell activation defect in common variable immunodeficiency: restoration by phorbol myristate acetate (PMA) or allogeneic macrophages.

Common variable immunodeficiency (CVI) represents a group of familial and sporadic diseases characterized by a range of B-cell, T-cell, and macrophage defects. A defect in T-cell activation, involving reduced proliferation and IL-2 production after stimulation with OKT3 antibody, has been described previously. In the present study we found that these defects could be corrected in vitro by adding phorbol myristate acetate (PMA) to OKT3-stimulated peripheral blood mononuclear cells (PBMC) of 14 patients with CVI. PBMC of 6 out of 7 patients with CVI studied also exhibited a profound defect in IL-2 receptor expression when incubated with OKT3 antibody. IL-2 receptor expression after stimulation with PMA alone was normal, indicating that the OKT3- but not the PMA-induced pathway of IL-2 receptor expression was defective. On the RNA level, the genes for IL-2 and IL-2 receptor were expressed after stimulation with OKT3 antibody. IL-2 and IL-2 receptor gene expression were normal, indicating a possible post-transcriptional defect. To investigate whether the defect in T-cell activation was at the macrophage or the T-cell level, we prepared adherent cells and monocyte-depleted T cells (E+) from 3 patients with CVI and from normal blood donors. Incubating CVI E+ cells with normal adherent cells resulted in normal proliferation and IL-2 production in the presence of OKT3, whereas incubation of normal E+ cells with adherent cells from patients with CVI under the same conditions showed reduced IL-2 production and proliferation, suggesting the macrophage as the origin of the failure in T-cell activation in the patients with CVI studied. Inhibition by macrophage-secreted prostaglandins was excluded by failure to correct the IL-2 production and proliferation defects in the presence of indomethacin.

Adult↗
PubMed1986

Dietary bovine antigens and immune complex formation after intravenous immunoglobulin in common varied immunodeficiency.

Previously we have shown that the sera of hypogammaglobulinemic patients may contain large amounts of antigenically intact foreign protein of dietary origin, presumably due to the absence of an adequate gastrointestinal secretory immune barrier. In these studies we show that the intravenous infusion of immunoglobulin in these patients may result in high levels of immune complexes postinfusion and that at least one constituent of these complexes is likely to be bovine casein.

Agammaglobulinemia↗
PubMed1986

Modulation of the immune response by immunoglobulin for intravenous use. II. Inhibitory effects of sera from treated patients.

Sera were collected from patients with common varied immunodeficiency (CVI) prior to and following intravenous gamma-globulin (IVGG) infusion. Cultures of pokeweed mitogen (PWM)-stimulated peripheral blood mononuclear cells from normal donors in medium containing post-IVGG infusion sera generated significantly fewer plaque-forming cells (PFC) than those cultures in medium containing the corresponding pre-IVGG infusion sera. However, preinfusion CVI sera were found to be similar to normal sera in their capacities to support PWM-induced PFC generation, despite the disparity in Ig levels between the two groups of sera. Furthermore, serum collected from a CVI patient 24 hr or more after IVGG infusion no longer possessed the same inhibitory capacity as serum collected 10 min after IVGG infusion despite elevated IgG levels compared to baseline. These studies suggest that IVGG infusion may induce an immunosuppressive effect which is transient in nature, raising the possibility of in vivo counterbalancing homeostatic mechanisms responding to this immune perturbation.

Antibody-Producing Cells↗
PubMed1986

Use of an IgA-depleted intravenous immunoglobulin in a patient with an anti-IgA antibody.

In this report we describe the use of an IgA-depleted preparation of intravenous gamma-globulin in a patient with hypogammaglobulinemia and an anti-IgA antibody. An IgA containing intravenous gamma-globulin had previously produced anaphylactoid reactions, immune complex formation, and complement activation. The patient has had no reactions to the IgA-depleted preparation after 18 months of treatment; immune complex formation and complement activation have not been demonstrated, and the titer of antibody to IgA has diminished.

Agammaglobulinemia↗
PubMed1986

Natural killer cell function and interferon generation in patients with primary immunodeficiencies.

Patients with primary immunodeficiency disorders were evaluated for three aspects of natural defense: natural killer (NK) cells which lyse HSV-infected fibroblasts [NK(HSV-FS)], NK cells which lyse K562 tumor targets [NK(K562)], and interferon-alpha generation. In addition, capacity to make interferon upon challenge with other commonly used inducers was also evaluated. Most patients with severe combined immunodeficiency disease (SCID) and deficits of both T- and B-cell function demonstrated normal NK function with one or both targets. Six of eight SCID patients generated interferon-alpha at or below the lower limit of normal while only two made clearly normal levels. Six of 10 patients with Wiskott-Aldrich syndrome (WAS) had normal NK(K562) and five of 10 generated normal levels of interferon-alpha but all had severely deficient NK(HSV-FS). Patients with Bruton's agammaglobulinemia demonstrated normal NK and interferon generation, as did patients with common variable immunodeficiency, even when subdivided into patients with T-cell proliferative deficiencies and those with only hypogammaglobulinemia. Natural defense parameters may help categorize patients with SCID and WAS and help define these heterogeneous diseases.

Agammaglobulinemia↗
PubMed1986

Immune complex glomerulopathy in a child with food hypersensitivity.

This report describes the occurrence of immune complex glomerulonephritis in a patient with eosinophilic gastroenteritis and food hypersensitivity. A coincident allergen injection may have been a contributing factor in the sudden development of the nephrotic syndrome. Markedly elevated levels of circulating immune complexes (greater than 6400 mg/dl) were found containing kappa-casein and bovine serum albumin (BSA), the latter predominating. Markedly elevated serum BSA hemagglutinating titers were also present (1:40,960). Cross-reacting precipitating antibodies to BSA, beef, and pork were demonstrated, but not to flounder or ovalbumin. Renal biopsy revealed immune complex glomerulonephritis with BSA, immunoglobulins M and G and complement deposited focally in the glomerular basement membrane. With strict dietary limitation of identified causative antigens and prednisone therapy, CIC levels decreased to 16,000 micrograms/dl and serum BSA antibody hemagglutinating titer fell 32-fold over a period of 15 months. There was prompt symptomatic relief and amelioration of signs of nephritis. The patient was able to consume a diet normal in protein and caloric content, and statural catch-up growth occurred. Recognition of food antigens to which the patient was hypersensitive provided a rationale for the relief of the gastrointestinal disturbance, growth stunting, and renal disease.

Adolescent↗
PubMed1986

Intravenous treatment of autoimmune hemolytic anemia with very high dose gammaglobulin.

Autoimmune hemolytic anemia (AIHA) has been considered to be unresponsive to intravenous gammaglobulin (IVGG) at the doses that are effective in immune thrombocytopenic purpura and autoimmune neutropenia (usually 2 g/kg total dose). This study reports the use of a higher dose (5 g/kg total dose over 5 days) in four severe cases of AIHA which resulted in a sustained remission in two patients, a transient response in the third, and a failure in the forth patient. These data suggest that larger quantities of IVGG may be needed in this disease, possibly because the reticuloendothelial system appears to be enlarged in AIHA patients.

Adult↗
PubMed1986

Treatment of AB deficiencies.

The objective of this study was to compare serum immunoglobulin levels and the clinical status of patients with primary immune deficiency who received an intravenous immunoglobulin (IVIG) (pH 4.0) preparation for 1 year with results previously obtained when the same patients received intramuscular immunoglobulin (IMIG). During the IVIG treatment year, increased serum immunoglobulin levels, shorter duration of certain infectious disorders, reduced antibiotic use, ans improved rheumatoid symptoms were observed. The actual benefit of IVIG therapy could not be established until after the sixth months, since illness was even further reduced during the second 6 months of treatment. Other clinical observations are evaluated in the 2 groups.

Anti-Bacterial Agents↗
PubMed1986

C1 esterase inhibitor deficiency in X-linked hypogammaglobulinaemia: an anomaly fostering anaphylactoid reactions following intramuscular gammaglobulin administration.

A patient with apparent X-linked agammaglobulinaemia was found to be inordinately susceptible to anaphylactoid reactions to intramuscular injections of gammaglobulin. The patient was found also to have low levels of C1 esterase inhibitor (C1 INH). The possibility that the C1 INH deficiency and in this patient, whether genetic or acquired, fostered the susceptibility to the production of anaphylactoid reactions after gammaglobulin injections urges further studies of the association of C1 INH deficiency and anaphylactoid reactions to gammaglobulin injections. The possibility that C1 INH levels like C1q levels may be low in hypogammaglobulinaemic patients as a consequence of increased catabolism of this regulator of the complement system when IgG levels are low is considered.

Adult↗
PubMed1986

Association of circulating immune complexes containing bovine proteins and graft-versus-host disease.

Chronic graft-versus-host disease (GVHD) is a complex immunological disease which can appear in up to 30% of survivors of allogeneic bone marrow transplantation. Target organs include skin, mucous membranes and liver; eventual mucosal defects, specifically involving secretory IgA, have been observed. In these studies we show that transplant recipients who develop GVHD are more likely to have higher serum antibody titres to bovine casein and circulating immune complexes containing casein than patients who do not develop this complication. The stage of GVHD may be related to the level of antibody to casein. The biological role of immune complexes in relationship to the evolution of this disease is unknown.

Acute Disease↗
PubMed1986

Analysis of the gastrointestinal secretory immune barrier in IgA deficiency.

Secretory IgA is known to play a major role in the exclusion of foreign antigens from the systemic compartments. We have previously shown that IgA-deficient subjects can have large amounts of circulating immune complexes containing bovine antigens of dietary origin, presumably due to the defective secretory barrier. In these studies, we investigated whether the peak amount of immune complexes found after specific antigen challenge could be related to the level of serum or salivary IgA. Our data show that the peak of immune complex is not related to either serum or salivary IgA but that it is closely correlated to the titer of antibody to milk proteins. In addition, it appears that some individuals with only modest IgA deficits can have substantial mucosal permeability defects on milk challenge.

Adolescent↗
PubMed1986

Recurrent knee pyarthrosis with intact hyaline cartilage. A case report.

A 20-year-old patient with hyperimmunoglobulin E and abnormal leukocyte chemotaxis was treated by synovectomy for chronic and recurrent staphylococcal knee pyarthrosis. The articular cartilage was noted to be preserved despite the severity of synovial involvement and the chronic nature of this case of septic arthritis. Polymorphonuclear leukocytes were few, despite florid Staphylococcus aureus growth. This observation lends support to the role of lysozomal enzyme activity from leukocytes in hyaline cartilage damage in pyarthrosis.

Adult↗