Lower Serum IgG Levels Research Articles

Selective suppression of IgG2a subclass in LEC rats during development

The LEC rat is a mutant strain that has been established as a model of hepatitis and hepatoma. In addition to hepatic disorders, it has been found that this strain has a defect in T cell maturation, and has low levels of serum IgG. Sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot analysis showed that low levels of serum IgG were largely due to reduction of the IgG2a subclass. Quantitative determination of IgG subclasses by enzyme-linked immunosorbent assay (ELISA) using subclass-specific antibodies indicated that IgG2b and IgG2c subclasses were increased during development in this strain, whereas the IgG2a subclass was markedly decreased. These results suggest the dysfunction of some helper T cells in LEC rats selectively suppress synthesis of the IgG2a subclass during development but not affect production of IgG2b and IgG2c.

Plasma proteins and lymphocyte phenotypes in long‐term plasma donors

The possible effects of long-term plasma donation remain unknown, but it is important to investigate them so that donor safety is ensured. The purpose of this study was to determine if long-term plasma donation alters plasma proteins or lymphocyte phenotypes. Two groups of long-term plasma donors, source plasma donors (n = 20) and Rh immune globulin plasma donors (n = 26), were compared with whole blood donors (n = 29) and nondonor controls (n = 30). Blood samples were obtained prior to donation. Serum protein, albumin, globulin, and immunoglobulin levels were determined. In an assay using whole blood, lymphocyte phenotypes were characterized with a panel of single- and dual-labeled monoclonal antibodies and subsequent analysis by flow cytometry. As compared to the nondonor controls and/or whole blood donors, the mean values for serum protein, globulin, and IgG levels were lower in both plasma donor groups, with a significant negative correlation between donation frequency and serum protein values for the source plasma donors. Albumin levels were within normal ranges for both groups of plasma donors. No significant differences existed among the donor groups in total white cell counts, the percentage or absolute number of lymphocytes, T (CD3) cells, or helper T (CD4) cells. However, there were increased percentages of B (CD19) cells and decreased percentages of suppressor T (CD8+/CD11b+) cells and natural killer cells in both groups of plasma donors as compared to nondonor controls. Many plasma donors have low levels of serum protein, globulin, and IgG. In addition, they have increased percentages of B cells and decreased percentages of suppressor T and natural killer cells. The clinical significance of these findings warrants further investigation.

IgG subclass levels in patients with B cell chronic lymphocytic leukaemia.

Patients with B-cell chronic lymphocytic leukaemia (BCLL) have low levels of serum IgG. In order to determine if this is a pan IgG deficiency or a selective suppression of one or more IgG subclasses, levels of IgG 1, 2, 3 and 4 in nine BCLL patients were determined and compared to those of nine age and sex matched controls. No significant differences were found in the levels of IgG1 and IgG2, but the patients were found to have significantly lower levels of IgG3 (p < 0.05) and IgG4 (p < 0.05). Selective deficiencies of these isotypes may explain the particular pattern of infection seen in BCLL patients.

Targeted Immunoglobulin Therapy for the Prevention of Neonatal Infections

Premature infants demonstrate hypoglobulinemia and are at increased risk for serious infections. Although a cause-and-effect relation between low serum IgG levels and neonatal infections has not been established, prophylaxis of such severe infections may be possible by replacement of antibody with intravenous immunoglobulin (IVIG). For success, IVIG must provide specific antibodies to neonatal pathogens and reach therapeutic serum IgG target levels. Pilot investigations have demonstrated that IVIG reduces the incidence of bacterial sepsis among premature infants. Infants received IVIG every 2 weeks (or more frequently) until they weighed 2,000 g. Serum IgG levels were monitored after each dose so that the dose could be adjusted to achieve a target IgG level greater than 700 mg/dL. The observation that infection among placebo-treated patients occurred when the serum IgG level declined to less than 400 mg/dL suggests the importance of achieving a target level. In our preliminary analysis, the IVIG used did not reduce the incidence of infection with respiratory syncytial virus (RSV) and rotavirus or of necrotizing enterocolitis. That the lot of IVIG used did not contain significant antibody to RSV or rotavirus emphasizes the importance of pathogen-specific antibody. Because of the preliminary nature of these results and the potential for undetermined short-term and long-term sequelae, we do not recommend the indiscriminant use of IVIG for prevention or treatment of neonatal infections.

Absent specific viral antibodies in patients with transient hypogammaglobulinemia of infancy

Of 247 patients referred to the Pediatric Immunology Clinic, University of Connecticut Health Center, Farmington, Conn., for recurrent infections, 13 patients were found to have an abnormal delay in the onset of IgG synthesis and prolongation of the physiologic hypogammaglobulinemia of infancy. At first observation, their mean age was 10.6 months. All patients had abnormally low serum IgG levels (⩽2 SD for their age). The mean serum IgG level for our patient population was 270 ± 81 mg/dl; the mean serum IgG level of the control group was 749 ± 440 mg/dl. Clinically, these patients were first observed with recurrent otitis media, respiratory infections, bronchitis and/or asthma, and formula intolerance. Despite recurrent respiratory tract infections, specific antibodies to the respiratory viruses were absent in nine of 11 patients tested who were observed before 17 months of age. On follow-up, two of the 13 patients never developed specific antibodies to viral agents, although their serum IgG levels normalized; one patient became serology positive at the same time that the serum IgG normalized. In two patients, the serum IgG levels returned to within the normal range for age before the appearance of specific viral antibodies. In eight patients, the appearance of specific viral antibodies was detected before the serum IgG levels returned to normal. Five of these eight patients were treated for short periods (9 months) with replacement immune serum globulin (intramuscular) therapy and did clinically well. These observations suggest that replacement immune serum globulin for short periods of time does not appear to suppress the production of specific, naturally occurring antibodies and the resolution of the hypogammaglobulinemia.

ＩｇＧサブクラス低下の４症例

Immunodeficiency syndromes are considered to be responsible for some intractable infections of the ear, nose or throat.In Japan, however, there have been only a few reports of IgG subclass deficiency.This is a report of four cases of chronic or recurrent respiratory infection considered to be related to low serum levels of IgG subclass.In two patients with purulent rhinorrhea and productive cough the diagnosis was chronic sinusitis, bronchiectasis and OME. Haemophilus influenza was isolated in sputum cultures. One patient had selective IgG2 deficiency and the other patient had a low serum IgG4.The third patient had prolonged otitis media, had low serum IgG3 and a diagnosis of Prader-Willi syndrome, the fourth had recurrent otitis media, low serum IgG4 and a diagnosis of Wiskott-Aldrich syndrome.Monthly intravenous injections of human immunoglobulin with high concentrations of the deficient subclass and appropriate antibiotic therapy brought about cures of their infections.

Low serum levels of IgG- and IgM-rheumatoid factors in patients with idiopathic membranous nephropathy.

Low serum levels of IgG- and IgM-rheumatoid factors in patients with idiopathic membranous nephropathy.

The biological correlates of psychological responses to breast cancer

A prospective, multidisciplinary, 5 year study of 69 consecutive women with early breast cancer was conducted. Patients' psychological responses to the diagnosis were assessed 3 months post- operatively and correlated with various histological, mammographic, hormonal and immunological investigations performed pre-operatively and at 3 months post-operatively. There was no statistically significant association between the type of psychological response and any of the biological measures studied pre-operatively. There is, therefore, no evidence that biological factors have biased the composition of the groups and accounted for observed differences in outcome. Serum levels of IgM, performed 3 months post-operatively, however, were significantly higher in patients who showed denial compared to those who responded with fighting spirit ( p < 0.02) or stoic acceptance ( p < 0.02). Also patients who showed fighting spirit had significantly lower serum levels of IgG than those who showed stoic acceptance ( p < 0.025). The mechanisms by which such immunoglobulin changes could influence survival in cancer remain hypothetical. A greater understanding of the neuroendocrine control of the immune system and much more sophisticated measurements will be needed to elucidate such mechanisms.

Pneumococcal infections after human bone-marrow transplantation.

Seven of 26 long-term survivors (greater than 7 months post-transplant) of bone-marrow transplantation developed penicillin-sensitive pneumococcal infections more than 7 months after transplantation. One patient had two infections. Six of eight infections were associated with pneumococcal bacteremia, and Streptococcus pneumoniae type 6A was isolated in three cases. Two infections were fatal. All patients had normal nematopoietic function, and none was receiving immunosuppressive therapy. The development of pneumococcal infection was significantly associated with males and with abnormally low or high serum IGG and IgM levels but not with graft-versus-host disease. Serum opsonic activity for S. pneumoniae type 6A was decreased in six of the seven patients when compared to normal pooled serum in an in-vitro bactericidal assay. Four of the six patients with impaired opsonic activity had low serum antibody levels for S. pneumoniae type 6A capsular polysaccharide, while the other two patients had low serum CH100 complement activity. Bone-marrow transplant recipients have an increased susceptibility to pneumococcal infections and should be evaluated for prophylactic penicillin or pneumococcal vaccination.

Idiopathic late-onset immunoglobulin deficiency with associated defect in cell-mediated immunity.

An 8-year-old boy presented with idiopathic late-onset immunoglobulin deficiency manifested principally by recurrent suppurative chest infections and chronic diarrhoea with malabsorption. Nodular lymphoid hyperplasia and giardiasis were shown on small bowel biopsy. Investigation of the immune system showed low serum levels of IgG, IgM, and IgA, negative skin tests to four recall antigens, absent mixed lymphocyte reactivity, and impared lymphocyte responses to mitogens in vitro. Serum complement and granulocyte function studies were normal. Maintenance therapy with gammaglobulin and antibiotics gave a good response.

Immunodeficiency in Patients with Non-Hodgkin Lymphomas

Seventy-one previously untreated patients with non-Hodgkin lymphomas were studied with several readilyvailable tests of immune function: number of peripheral blood lymphocytes, serum immunoglobulins, and delayed hypersensitivity to six recall antigens. The results were correlated to histology (Rappaport classification), stage (Ann Arbor classification), the presence of symptoms, and survival. As a group, 38 patients with diffuse lymphomas exhibited marked impairment in reactivity to five of six antigens (p less than 0.03 to p less than 0.001). In addition, lymphopenia and reduced levels of serum IgA were found in association with diffuse histiocytic lymphoma. Among patients with diffuse lymphoma, lymphocyte number and skin test reactivity tended to be greater in those with localized disease or without constitutional symptoms, and survival was superior for patients free of symptoms (p less than 0.01). As a group, 33 patients with nodular lymphoma had normal numbers of lymphocytes, lower levels of serum IgG and IgA, and significant impairment of reactivity to two antigens (streptokinase-streptodornase and mumps; p less than 0.01); reactivity to three other antigens (Candida albicans, coccidiodin, and tuberculin) was normal. Survival for patients with nodular lymphoma was superior (p less than 0.01) compared to those with diffuse lymphomas. In summary, severe immunodeficiency was found in patients with diffuse lymphoma (particularly diffuse histiocytic lymphoma), and definite but much less severe immunodeficiency was characteristic of patients with nodular lymphoma.

Immunodeficiency in patients with non-Hodgkin lymphomas

Seventy-one previously untreated patients with non-Hodgkin lymphomas were studied with several readilyvailable tests of immune function: number of peripheral blood lymphocytes, serum immunoglobulins, and delayed hypersensitivity to six recall antigens. The results were correlated to histology (Rappaport classification), stage (Ann Arbor classification), the presence of symptoms, and survival. As a group, 38 patients with diffuse lymphomas exhibited marked impairment in reactivity to five of six antigens (p less than 0.03 to p less than 0.001). In addition, lymphopenia and reduced levels of serum IgA were found in association with diffuse histiocytic lymphoma. Among patients with diffuse lymphoma, lymphocyte number and skin test reactivity tended to be greater in those with localized disease or without constitutional symptoms, and survival was superior for patients free of symptoms (p less than 0.01). As a group, 33 patients with nodular lymphoma had normal numbers of lymphocytes, lower levels of serum IgG and IgA, and significant impairment of reactivity to two antigens (streptokinase-streptodornase and mumps; p less than 0.01); reactivity to three other antigens (Candida albicans, coccidiodin, and tuberculin) was normal. Survival for patients with nodular lymphoma was superior (p less than 0.01) compared to those with diffuse lymphomas. In summary, severe immunodeficiency was found in patients with diffuse lymphoma (particularly diffuse histiocytic lymphoma), and definite but much less severe immunodeficiency was characteristic of patients with nodular lymphoma.

IgG ANTIBODIES TO IgA IN TWO PATIENTS WITH HYPOGAMMAGLOBULINAEMIA TREATED WITH COMMERCIAL GAMMAGLOBULIN

Antibodies to IgA were detected in two males with hypogammaglobulinaemia. The antibodies were demonstrated to belong to the IgG class. In both patients low serum levels of IgG and IgM but no IgA were found. On two occasions one of the patients reacted with severe side reactions within a few seconds after an intramuscularly given injection of gammaglobulin. The other patient had received monthly intramuscular injections of gammaglobulin over a period of 2 years when the anti‐IgA antibodies first appeared and has since then been regularly treated for 1 1/2 years without any signs of adverse reactions. In five additional patients with hypogammaglobulinaemia and side reactions after i.m. injections of gammaglobulin no antibodies to IgA, IgG or Gm‐determinants were detected.

Functional and morphological observations on the effect of cyclophosphamide on the immune response of the chicken.

SummaryThe functional and morphological effects of cyclophosphamide (Cy) on the immune response of the chicken were investigated. Chickens given Cy on clays 1, 2 and 4 after hatching failed to produce antibody for at least 6 weeks and had low levels of serum IgG. Birds surviving for more than 6 weeks recovered their immunocompetence. The effect of Cy on cell‐mediated immunity (CMI) was less persistent. Allogeneic skin grafts applied to one‐week‐old treated birds were not rejected but grafts were rejected from 3‐week‐old recipients. At no time was graft versus host activity completely eliminated by Cy treatment.Morphological changes in the lymphoid organs reflected the results of functional tests. Early after treatment, lymphocytes were eliminated from thymus, bursa and spleen. Lymphoid regeneration usually occurred in the thymus by 3 weeks after treatment. Bursal regeneration was observed less frequently, and usually only in birds older than 6 weeks. In many birds, chronic degenerative changes in the epithelial cells were apparent, especially in the bursa.It was speculated that in those birds where thymus or bursa regeneration failed to occur there was damage to the epithelial component of the organs. Possibly the bursal epithelial cells were more susceptible to the action of Cy than were thymic epithelial cells.

Immunoglobulins in infants of rubella-exposed mothers

Noninfected infants of women who received large doses of gamma globulin early in pregnancy for the prevention of rubella were found to have lower serum IgG levels than normal controls up until 1 year of age. This effect, however, did not create clinical problems. Infected babies, as defined by the presence of rubella antibody persisting beyond 5 months of age, had higher serum IgM and IgG concentrations than noninfected babies until age 2 years.