Defective Antibody Production Research Articles

Intravenous usage of gammaglobulin: humoral immunodeficiency, immune thrombocytopenic purpura, and newer indications.

Intravenous gammaglobulin is effective therapy of ITP and other autoantibody-mediated immune cytopenias. All children as well as adults unresponsive to splenectomy or with known immune deficiency are probably the best candidates for treatment with IVGG. Its major advantage, in addition to its efficacy of treatment and possible remission-inducing effect, is that it has the fewest side effects of any treatment of ITP so that it is the best maintenance therapy of patients when effective. Future uses of IVGG remain to be determined. Premature infants with a high mortality from sepsis and with hypogammaglobulinemia due to termination of pregnancy prior to transplacental antibody transfer may benefit from IVGG. A preliminary study suggested such benefit and also showed safety of IVGG treatment in that there was no impaired immune responsiveness of these prematures at 2 years of age (28). Another potential usage of IVGG involves the treatment of the hypogammaglobulinemia associated with certain types of malignancy. Patients with CLL, especially in the advanced stages, are often hypogammaglobulinemic. Multiple myeloma and Waldenstrom's macroglobulinemia are two other B-cell malignancies associated with antibody production defects which might benefit from antibody replacement therapy. Therapeutic IgG levels may be harder to obtain due to hypercatabolism of immunoglobulin. The issue of immune hyporesponsiveness during intensive chemotherapy is also unexplored. Secondary antibody responses do not seem to be impaired, but primary responses, as tested in numerous immunization studies, are decidedly impaired. Certain protocols, especially those treating high-risk acute leukemias and neuroblastoma during induction therapy are intensive with high rates of sepsis, and may warrant trials of prophylactic IVGG. Similarly, some form of humoral prophylaxis is becoming an important part of the handling of the patient undergoing bone marrow transplantation not only to prevent bacterial sepsis but also to prevent cytomegalovirus (CMV) interstitial pneumonitis. A likely additional usage is gammaglobulin replacement for patients undergoing plasmapheresis, especially if performed multiple times. Finally, the broad spectrum of antibacterial and antiviral antibodies present in the preparations (such as anti-CMV, anti-Group B strep, and antiendotoxin) and the ease and safety of delivery allow the preparations to be used in situations where a hyperimmune preparation might be desired and/or where more than one pathogen is possible. In summary, IVGG is a treatment capable of safely conferring significant benefits to selected patients.(ABSTRACT TRUNCATED AT 400 WORDS)

B cell function in acute malaria.

The development of protective immunity to malaria in humans is slow and incomplete1. Specific antibody responses to parasite antigens are an important component of protective immunity to parasites1. However, secondary humoral immunodeficiency which is known to occur in human and experimental malaria2 may prejudice the development of effective immunity to this parasite and may also contribute to the susceptibility of children living in endemic areas to infection by other microbial pathogens. The cellular mechanisms contributing to defective antibody production in malaria are incompletely understood2. The study of humoral immunosuppression in malaria in endemic areas is complicated by the coexistence of malnutrition and other parasitic diseases, both of which could contribute to the state of anergy. This study investigates possible cellular mechanisms of impaired antibody production in UK residents having acute attacks of malaria.

Susceptibility to coccidiosis: effect of strain of mouse on reproduction of Eimeria vermiformis.

The reproduction of Eimeria vermiformis in different strains of phenotypically normal mice and in mice with various immunological characteristics or defects was compared. In some strains of phenotypically normal mice there were marked differences in oocyst production, both in terms of numbers and in the duration of patency, allowing the strains to be classified as resistant or susceptible to infection with E. vermiformis. These differences were apparent only in primary infections; both types of strain were equally resistant to reinfection. Amongst the strains of mice with immunological deficiencies, reproduction of the parasite was greatest in the athymic (nu/nu) mutants and these mice were completely susceptible to reinfection. Strains of mice with lowered or defective antibody production, or with defective neutrophils and low NK cell activity (bg/bg) were more susceptible than the relevant controls to primary infection but all developed substantial immunity to reinfection. Asplenic (Dh/+) mutants were remarkably resistant to infection.

Protein deprivation causes reversible impairment of mucosal immune response to cholera toxoid/toxin in rat gut

Scretory antibodies may be the major defence against mucosal infections, especially those due to viruses and non-invasive pathogens such as Vibrio cholerae and toxinogenic Escherichia coli. The high incidence of mucosal infections in malnourished protein-deficient children may result from defective antibody production, but evidence for this is conflicting. We report here that protein deficiency markedly impairs the mucosal immune reponse to cholera toxiod/toxin (CT), a protein antigen, in rats and that this impairment is rapidly reversed by refeeding.

Diagnosis of defects of antibody production.

Diagnosis of defects of antibody production.

Escherichia coli antibody: a screening test for immunodeficiency.

Six patients suffering from recurrent chest infections were found to lack antibodies to a pooled antigen obtained from six different serotypes of commensal Escherichia coli bacteria. All had normal serum IgG concentrations, but five subsequently benefited from regular gammaglobulin injections. We suggest that the absence of such E. coli antibodies usually indicates a clinically significant defect in antibody production. This simple screening test is of use in the diagnosis of primary and secondary immunodeficiency disorders.

Combined immune deficiency, autoantibody formation, and mucocutaneous candidiasis

A 6-year-old girl with chronic mucocutaneous candidiasis (MCC) and an immunologic deficiency syndrome was studied in detail over a period of 2 years. The patient had a severe defect in cell-mediated immunity characterized by failure to mount a 48-hr delayed response to a battery of intradermal skin tests, persistent lymphopenia, and failure to be sensitized with 1-chloro, 2,4-dinitro-benzene (DNCB). Her lymphocytes neither produced migratory inhibitory factor nor consistently responded with an increased 3H-thymidine uptake when placed in tissue culture medium with Candida antigen. There was no evidence of a circulating factor in the patient's plasma capable of inhibiting the incorporation of 3H-thymidine by homologous lymphocytes cultured in the presence of Candida albicans and other antigens. The patient had defective antibody production to some but not all antigens. She failed to produce protective tetanus toxoid antibody titers and remained Schick test positive despite repeated diphtheria, pertussis, and tetanus (DPT) injections. She also had defective antibody responses to repeated paratyphoid-typhoid injections and was found to have a low serum IgA level. This patient possessed autoantibodies against smooth muscle and parietal cells and an inconstant positive antilymphocytotoxic assay. Immunologically unrelated precipitin antibody systems against human and calf thymus were also demonstrated in the patient's serum. Eradication of the Candida infection with intravenous amphotericin B, although resulting in marked clinical improvement, did not alter the immunologic abnormalities.

Antibody response to cholera vaccine. Differences between depressed, schizophrenic, and normal subjects.

THE FACT that relatively few individuals who harbor potentially pathogenic microorganisms actually develop clinical disease reflects the balance that usually exists between the host and the infectious agent. Disruption of this host-parasite relationship may result from defects in antibody production, severe leukopenia, dysfunction of other known host defenses, or the administration of adrenocortical hormones. More commonly, the factors which predispose a particular individual to develop clinically apparent infection are unknown. The possibility that psychological factors might influence host susceptibility by modifying the physiological status of the individual has been reviewed elsewhere. 1 One approach to this problem has been to examine the incidence of somatic illnesses in psychiatric patients, 2 and other investigations have sought some measurable parameter which would reflect the relative resistance of such patients to infectious disease. 3-9 The present study is an attempt to evaluate the immunological

Capillary resistance in rheumatoid arthritis.

The presence of antibodies to cardiolipin was determined (by an ELISA) in 143 patients with primary immunodeficiency diseases. Thirty (21%) had raised anticardiolipin antibody levels compared with only three in 98 age matched controls. The highest prevalence of this autoantibody was found in the Wiskott-Aldrich syndrome. Patients with selective IgA deficiency also showed a high prevalence of this autoantibody (32%), while patients with severe defects in antibody production showed a low prevalence or did not have such autoantibodies. This study provides further evidence of the association between autoimmune phenomena and primary immunodeficiency diseases.