Serum Protein Electrophoresis May Be Used as a Screening Tool for Antibody Deficiency in Children and Adolescents.

Background: Patients with antibody deficiency may experience exceptionally long diagnostic delays, increasing the risk of life-threatening infections, end-organ damage, mortality, and health costs. Objective: This study aimed to analyze serum protein electrophoresis and verify the correlation between calculated globulin (CG, total protein minus albumin levels) or electrophoretically determined serum gamma globulin fraction (Gamma) with IgG levels in children and adolescents under 18 years old (yo). Methods: We analyzed serum protein electrophoresis (GC or Gamma) and IgG levels from 1215 children and adolescents under 18 yo, classified into 5 age groups. We verified the correlation between CG or Gamma with serum IgG levels. Results: Serum IgG levels varied according to age groups (from 4.3 ± 2.3 g/l in children under 6 months old to 11.4 ± 3.2 g/l in adolescents in the 10-<18 yo group). CG sensitivity and specificity to detect IgG below the reference range for all patients were 93.1% and 81.8%, respectively, and varied according to age group. Gamma sensitivity and specificity for all patients were 100% and 87.8%, respectively, and varied according to age group as well. We found serum IgG levels below the age reference level in 29 patients (2.4% of the cases) using CG or Gamma levels. Conclusion: Both CG and Gamma levels may be of utility as a screening tool for earlier diagnosis of antibody deficiency in children and adolescents under 18 yo.

Inmunodeficiencia común variable: hallazgos recientes sobre anormalidades celulares / Common variable immunodeficiency: recent findings in cellular abnormalities

La Inmunodeficiencia Común Variable (IDCV), también llamada hipogammaglobulinemia adquirida o disgammaglobulinemia, es un grupo heterogéneo de desórdenes que afecta a los linfocitos (L)T y a los LB. Constituye uno de los principales síndromes de deficiencia de anticuerpos, presenta una pérdida o disminución de la respuesta inmune humoral a antígenos específicos, particularmente polisacáridos capsulares bacterianos. Estos pacientes tienen una alta susceptibilidad a infecciones del tracto respiratorio y la IDCV tiene una estrecha relación con patologías tales como deficiencias de IgA y subclases de IgG. El objetivo de esta revisión es actualizar los conocimientos de este grupo de desórdenes inmunológicos, con especial énfasis en los nuevos criterios utilizados para el diagnóstico y seguimiento (AU)

Síndrome de malabsorción por disgammaglobulinemia y alteraciones en inmunidad celular / Malabsorption syndrome for dysgammaglobulinemia and alternations in celular inmunity

Los síndromes de malabsorción intestinal tienen etiología múltiple; desde causas de origen sistémico hasta lesiones debidas a parasitosis, bacterias y otras de origen local. En el presente trabajo se hace una descripción de una causa poco frecuente pero muy interesante que es la malabsorción debida a disgammaglobulinemia la cual se caracteriza, según los trabajos clásicos, básicamente por un cuadro de diarrea crónico o intermitente; con períodos de esteatorrea; infección por Lamblia intestinalis y una incidencia muy alta de infecciones sinopulmonares. Desde el punto de vista inmunológico hay una disminución de las inmunoglobulinas del tipo IgA o IgM a nivel sérico y a nivel local; lo cual se describió en el estudio clínico de los pacientes. Además de las alteraciones antes mencionadas en estos pacientes, se demostró, por medio de los estudios inmunológicos, importantes defectos en la inmunidad celular, hechos aún no descritos en la literatura. Encontramos hiperestimulación en los linfocitos T cooperadores (TH) con normalidad en los linfocitos B; una sobreproducción de interleucina 2 (IL2) y una importante disminución en la función de las células NK (National Killer); lo cual puede estar en relación con la mayor incidencia de tumores de esta entidad

Deficiency of IgG4 in children: association of isolated IgG4 deficiency with recurrent respiratory tract infection.

To study the relationship between serum IgG subclass deficiency and clinical host defense impairment, we reviewed the clinical and immunologic features of 123 patients with a history of recurrent infection who had been examined for immunodeficiency in our laboratory (group 1). We then compared immunoglobulin isotype levels with those in sera from 127 age-matched control subjects without recurrent infection from whom blood had been drawn for evaluation of atopy (group 2). There was a significantly higher prevalence of IgG4 deficiencies among patients with recurrent infections (17% vs 7%; p less than 0.02), solely because of a higher prevalence of isolated IgG4 deficiency (n = 9; 7.3%) than in atopic control subjects (n = 1; 0.8%; p less than 0.05); there was a comparable prevalence of multiple isotype deficiencies that included low levels of IgG4 (9.8% and 6.3%, respectively). All nine group 1 patients with isolated IgG4 deficiency had severe recurrent respiratory tract infections requiring multiple hospitalizations; in addition, five were atopic, five had asthma, and one had chronic diahrrea. Antibody responses to bacterial polysaccharide antigens were normal for age in all patients with isolated IgG4 deficiency; two had defective antibody responses to protein antigens. Isolated IgG4 deficiency appears to be associated with impaired respiratory tract defenses and may occur in the absence of an easily definable antibody deficiency state. This association suggests a physiologic defense role for mucosal IgG4.

Subnormal serum concentrations of IgG2 in children with frequent infections associated with varied patterns of immunologic dysfunction.

To characterize more fully the immunologic basis for increased susceptibility to infection in patients with low serum concentrations of IgG2, we identified eight infection-prone children, 1 to 2 years of age, with serum IgG2 concentrations greater than 2 SD below the mean for age and followed their serologic and clinical courses for 1 to 3 years. Two of the eight children became clinically and immunologically normal and may have had transient IgG2 deficiency with an exaggerated developmental delay of this late-maturing subclass. The remaining six subjects had persistently subnormal or low-normal serum IgG2 levels and continued to experience frequent infections. All six of these children responded poorly to Haemophilus influenzae type b (Hib) polysaccharide, and four of six responded poorly to Streptococcus pneumoniae type 3 polysaccharide. Both IgG1 and IgG2-specific antibody responses to these vaccines were abnormal. Three of these six children also responded poorly to tetanus toxoid, an antigen that normally induces a predominant IgG1 response. Although five of these six children produced antibodies in response to Hib polysaccharide protein conjugate vaccine, three of four given Hib oligosaccharide CRM conjugate vaccine required booster doses to respond, a pattern of response characteristic of infants less than 6 months of age. Further, although serum concentrations of IgG1 were normal, peripheral blood mononuclear cells from four of six children tested produced extremely small amounts of IgG1 and IgG3 as well as IgG2. Finally, varied patterns of abnormalities of IgG, IgA, IgM, and IgG4 became apparent in five of the six children with persistently low serum IgG2 values. This study demonstrates that subnormal serum concentrations of IgG2 may be associated with varied patterns of immunologic dysfunction, some of which are evolving and may be responsible for increased susceptibility of these children to infection.

Protective immunity and eosinophilia in IgE-deficient SJA/9 mice infected with Nippostrongylus brasiliensis and Trichinella spiralis.

To elucidate the roles of IgE antibody in host responses to helminth infection, selective IgE-deficient SJA/9 mice were infected with the nematode parasites Nippostrongylus brasiliensis, which elicits remarkable potentiated IgE production, and Trichinella spiralis, which induces strong anti-Trichinella IgE antibody production in normal mice. The kinetics of blood eosinophilia, worm burden after primary infection, and resistance to secondary infection in SJA/9 mice were the same in both infections as those in congenic SJL/J mice used as an IgE-producing control. These results indicate that the host responses examined here operate under IgE-independent mechanisms.

Manifestations of milk allergy in infancy: clinical and immunologic findings.

In a study of the manifestations of cow milk allergy in 100 young children (mean age 16 months), 30 items of historical data and information relating to the effects of a standardized milk challenge were entered into a computer data base. Three clusters of patients were derived using a K-means algorithm. In group 1 were 27 patients with predominantly urticarial and angioedematous eruptions, which developed within 45 minutes of ingesting cow milk. They had positive skin test reactions to milk and elevated total and milk specific IgE serum antibody levels. In group 2, 53 patients had pallor, vomiting, or diarrhea between 45 minutes and 20 hours after milk ingestion. These children were relatively IgA deficient. The 20 patients in group 3 had eczematous or bronchitic or diarrheal symptoms; in 17 symptoms developed more than 20 hours after commencing milk ingestion. Of the patients in group 3, only those with eczema had a positive skin test reaction and elevated IgE antibodies to milk. The patients in group 3 were the most difficult to identify clinically; they had a history of chronic ill health, and symptoms developed many hours or days after commencing milk ingestion in the challenge situation. In view of the heterogeneous clinical and immunologic findings in our patients, it is unlikely that a single laboratory test will identify cow milk allergy in all susceptible patients.

Spectrum of IgG2 subclass deficiency in children with recurrent infections: prospective study.

Serum immunoglobulins and IgG subclasses were measured in 30 children with recurrent infections. Seven patients had low IgG2 concentrations (less than 3SD below the geometric mean for age). Four of these seven patients had normal concentrations of IgG, IgA and IgM, and thus would have been considered immunologically normal by routine criteria. The seven children with IgG2 deficiency had more severe infections than the 23 children with normal IgG2. Five children had recurrent pneumonia or sinusitis, one had recurrent invasive Haemophilus influenzae type b infections, and one had severe pneumococcal meningitis. Their immunologic abnormalities were heterogeneous. Two children had isolated IgG2 deficiency, two had IgG2-IgG4 deficiency, one had IgG2-IgG4-IgA deficiency, one had IgG2-IgA deficiency, and one had severe IgG1-IgG2 deficiency with abnormal T cell function and thrombocytopenia. Thus IgG2 deficiency occurs frequently among children with recurrent infections, and is associated with a variety of clinical and immunologic abnormalities.

Immunoregulatory defects in a family with selective IgA deficiency.

Defects in regulation of the humoral immune system were examined in a family with selective IgA deficiency. Two patients (mother and son) were clinically well and had selective abnormalities of B lymphocytes that can differentiate into IgA plasma cells plus specific T cell suppression of IgA production. One patient (daughter) had several clinical problems and received nine monthly transfusions of normal plasma. Prior to therapy, this patient had abnormal immunoregulation of both B and T lymphocyte population that cooperated in the formation of all cases of immunoglobulin-producing cells. After treatment, her clinical problems were resolved and her cellular abnormalities appeared identical in those in her mother and brother.

[Type III hyperlipoproteinemia--diabetes mellitus and dysglobulinemia]. / Hiperlipoproteinemia tipo III--diabétes mellitus y disglobulinemia.

This paper reports the association of diabetes mellitus and hyperlipidemia type III and the relation between the dose of insulin and the serum level of triglycerides and cholesterol. The coexistence of hiperglobulinemia, Bence Jones proteinuria and a positive rheumatoid factor is also reported.

Inflammatory myopathy, IgA deficiency, and intestinal malabsorption.

Two IgA-deficient children with inflammatory myopathy and intestinal malabsorption were evaluated. The myopathy was characterized by weakness of facial and proximal limb muscles, increased serum concentrations of lactic dehydrogenase and creatine phosphokinase, and histologic evidence of inflammation and degeneration of muscle fibers. Features of the intestinal abnormality were blunted villi, interstitial inflammation, and reduction in IgA-containing plasma cells and IgA content of epithelial cells. The myopathy and malabsorption improved with corticosteroid treatment. Circulating antibodies to striated muscle could not be demonstrated in either patient, but one had antibodies to milk and chicken serum proteins. We speculate that IgA deficiency may predispose to the development of inflammatory myopathy.