IgM Deficiency Research Articles

77.Isolated IgM deficiency

77.Isolated IgM deficiency

Chemotactic Function in the Human Neonate: Humoral and Cellular Aspects

Extract: The cellular and humoral components of the chemotactic response in neonates have been compared with those in adults. Leukocytes from neonates were compared with those from adults in their ability to movetoward chemotactic factors (CF) generated from pooled, normal serum. Neonatal leukocytes showed a consistent and highly significant deficiency in their response to chemotactic factor generated from Staphylococcus aureus, Escherichia coli, or albumin-antialbumin (Table I). Chemotactic factor generated from neonatal and adult sera was compared for its ability to stimulate migration of a standardized, normal leukocyte pool. A small but highly significant difference was seen between the amounts of effective CF generated from neonatal sera and that from adult sera. The difference was found with all three generating agents (Table II). The mechanism by which leukocytes undergo chemotactic migration is presently unclear. It is possible that in neonates cellular defects in leukocyte phagocytosis and leukotactic chemotaxis may be related to developmental immaturity of common biologic mechanisms. Although other serum factors may be involved, it appears that the separate deficiencies of neonatal sera in generation of CF and enhancement of phagocytosis may both be related to deficiencies of C3 and C5. The enhanced susceptibility to infection in neonates cannot be explained simply by a selective deficiency of IgM. Addition of IgM failed to correct the humoral deficiencies of chemotaxis and phagocytosis in vitro. Further, a deficiency of IgM would not explain the cellular deficiencies demonstrated. It is only by a sequential analysis of the entire inflammatory response in the neonate that these relations will become clear. Speculation: It has become apparent that the relative susceptibility of the neonate to bacterial infections is the result of a number of deficiencies involving both humoral and cellular aspects of the neonatal inflammatory response. The future delineation of these individual defects may lead to improved therapeutic approaches in neonatal septicemia and, also, provide valuable information on the mechanisms involved in the normal inflammatory response.

Metabolism of autologous 131-I-labelled IgG in patients after renal homo-transplantation.

1. The metabolism of autologous 131I-labelled IgG was studied in five patients after renal homotransplantation. Two patients had received grafts from related living donors and three from cadavers and all grafts were functioning. All five patients were on immunosuppressive therapy with prednisone and azathioprine. No episodes of rejection occurred during the study. 2. One patient had serum concentrations of IgG and IgA and IgM below normal; one had isolated IgM deficiency; one had isolated IgA deficiency; and two had increased serum IgM concentrations. 3. Plasma volume and distribution ratio were normal in all five patients; the plasma IgG pool was normal in four and significantly decreased in one. Fractional turnover rate was normal in four and increased in one; the plasma half life was normal in three and shortened in two. 4. The IgG synthesis rate was normal in two, at the lower limit of the normal range in two and decreased in one. There was no obvious correlation with the age of the patient, the dosage of prednisone or azathioprine, the incidence of infection, the survival and function of the graft or serum immunoglobulin concentrations.

Immunoglobulins and dietary protein antibodies in childhood coeliac disease

Twenty-four children with coeliac disease were compared with a control group, comprising 17 children with a variety of gastroenterological disorders, with respect to serum immunoglobulins and dietary protein antibodies. Elevated levels of IgA and abnormally low levels of IgM were demonstrated in one third of the coeliac patients. Antibodies to at least one of eight dietary proteins were found in 50% of coeliac children. Three children with raised levels of serum IgA and two with deficient IgM were re-examined after varying periods on a gluten-free diet. Antibodies to dietary proteins had waned and immunoglobulin levels returned to normal in all cases. The raised IgA was considered to have resulted from an extensive immunological response to antigens of dietary origin which had entered through the abnormal gut mucosa. It is suggested that IgM deficiency was due to specific inhibition of IgM synthesis by dietary components which had also entered through the mucosa.

Some relationships between serum immunoglobulin deficiencies and infection in utero and in the early weeks of life

Abnormal intrauterine antigen stimulus, by viruses or by other antigens, may lead to abnormal maturity of immunity mechanisms, which may be recognized by raised serum IgM and IgA in the first days of life and also, in congenital rubella, to IgG deficiency. The latter can also be induced by neonatal antigen stimulus in mice by nonreplicating antigens. Abnormal susceptibility to virus infection, including progressive necrotic vaccinia, is usually associated with cellular immunity deficiency. Disseminated nonprogressive vaccinia, which occurred in nearly 1 per 1,000 of a population, is associated with significant deficiency of IgM and IgA, without evidence of deficiency of cellular immunity. This may parallel the apparent special role of IgM in protection against meningitis. Partial and transient immunoglobulin deficiencies may occur in symptomless relatives of patients with more severe immunity deficiency states. Estimation of immunoglobulins in relatives of patients with diseases such as leukemia, in which both vertically transmitted virus infection and familial immunity deficiency may play a part, provides a valuable nonspecific measure for epidemiological studies.

Antibody deficiency syndrome and autoimmune haemolytic anaemia in a boy with isolated IgM deficiency dysimmunoglobulinaemia type 5.

SummaryThis paper describes a boy who suffered from severe recurrent infections from the first year of life. A brother with similar symptoms died from meningococcal meningitis. Virtually no IgM was demonstrable in the patient's serum, and it is suggested that the antibody deficiency syndrome in this case was based on a familial congenital disturbance in IgM synthesis. A study of antibody formation disclosed that disturbances existed in the formation of antibodies assumed to be contained in IgM; other antibodies were produced in adequate amounts. The significance of these findings is discussed in some detail. The boy subsequently developed autoimmune haemolytic anaemia. The question whether this was caused by the IgM deficiency or whether the immunological imbalance was based on a general disorder must remain unanswered.

Adult hypogammaglobulinemia with malabsorption and iron deficiency anemia

This thirty year old woman, who had had recurrent respiratory tract infections from age two, was found to have a severe deficiency of serum immunoglobulins IgG, IgA and IgM. She also had scant peripheral lymphoid tissue with only rare plasma cells. Functionally, she rejected a homograft in normal time. Delayed hypersensitivity was present only to mumps antigen. She failed to respond to typhoid vaccine with specific antibody, but a reaction to the Schick test was negative. Injected virus particles were cleared normally from the circulation despite very low specific antibody production. Jejunal villous atrophy, histologically similar to celiac sprue, was associated with impaired absorption of orally administered iron. No response to a gluten-free diet occurred histologically. One son lacked detectable serum IgA and the serum IgA of the other son was low. The maternal grandfather had a high serum IgA perhaps age-related. In all other family members immunoglobulin levels were normal. The association of immunoglobulin deficiency and malabsorption remains unexplained.

IgM DEFICIENCY WITH HYPERGAMMAGLOBULINAEMIA AND RECURRENT MONONUCLEOSIS

SYNOPSIS A case of hypergammaglobulinaemia, IgM and IgD deficiency, recurrent lymphadenppathy, and mononucleosis is described. Investigation revealed low titres of isohaemagglutinin and low levels of diphtheria antitoxin (neither of which responded to antigenic stimulation), slightly delayed rejection of skin homograft and anergy to tuberculin. The increased susceptibility to infection and the immunoglobulin abnormality were considered to be primary, and not secondary to acquired disease. Case reports of isolated IgM deficiency from the literature are briefly summarized, and some non-malignant causes of mononucleosis are mentioned.