Infants with low immunoglobulin levels: Isolated low IgA level vs other immunoglobulin abnormalities.

BACKGROUND: The International Union of Immunological Societies defined transient hypogammaglobulinemia of infancy as decreased IgG and IgA levels. Some others, however, include decreased IgA level alone. We compared infants with decreased levels of IgG and IgA, all isotypes, and IgA alone. OBJECTIVE: To determine whether infants presenting with diminished IgA only differ clinically and in time of immunoglobulin recovery, from those with decreased levels of IgG and IgA, or of all major isotypes. METHODS: Eighty-seven term infants found to have immunoglobulin isotype(s) 2 or more SDs below mean, normal antibody response, intact cellular immunity, and absence of other immunodeficiency syndrome features were evaluated between January 1, 1977 and December 31, 2008. Infants had decreased IgA level (group 1, n = 43), decreased IgA and IgG levels (group 2, n = 39), or low IgA, IgG, and IgM levels (group 3, n = 5). RESULTS: Groups had similar histories. Immunoglobulins normalized in a similar percentage of all groups during infancy but earlier for group 1 (P = .005). CONCLUSION: Little reason exists to separate infants with isolated decreased IgA levels from those with decreased levels of IgA and IgG or all isotypes.

Children with Tourette's syndrome may suffer immunoglobulin A dysgammaglobulinemia: preliminary report.

BACKGROUND: Postinfectious autoimmunity has been implicated in Tourette's syndrome and obsessive-compulsive disorder (TS/OCD), whereas increased frequency of upper respiratory tract infections (URTI) in TS/OCD patients suggests immune deficiency. We hypothesized that antineuronal antibodies may be elevated in patients (reflecting autoimmune processes), and levels of total immunoglobulins (Igs) may be decreased (reflecting immune deficiency). METHODS: We analyzed plasma of TS/OCD patients (n = 24) and healthy age- and sex-matched control subjects (n = 22) by enzyme-linked immunosorbent assay (ELISA) for the levels of total and specific IgG, IgM, and IgA against antigens previously identified in multiple sclerosis (myelin basic protein and myelin-associated glycoprotein) and Sydenham's chorea (ganglioside-GM1, lysoganglioside, and tubulin). RESULTS: Total IgA was decreased in TS/OCD patients (median 115 mg/100 mL) compared with control subjects (141 mg/100 mL; p = .02). Specific IgA against all antigens, except tubulin were also decreased in the patients (MPB 0 vs. 13 [ELISA units [EU]; myelin-associated glycoprotein 29 vs. 44 EU, p = .04; ganglioside GM1 21 vs. 35 EU, p = .01; lysoganglioside 44 vs. 56 EU, p = .03; tubulin 44 vs. 44 EU, p = .8). The levels of total IgA and anti-myelin basic protein (MBP) IgA were significantly lower in the subgroup of pediatric autoimmune neuropsychiatric disorder associated with Streptococcus (PANDAS) cases (n = 10) than in non-PANDAS cases (n = 9; total IgA 98 mg/100 mL vs. 133 mg/mL, p = .03; anti-MBP IgA 1 vs. 6 EU, p = .03) or healthy control subjects (total IgA 141 mg/100 mL, p = .02; anti-MBP IgA 13 EU, p = .005). CONCLUSIONS: At least some TS/OCD patients may suffer IgA dysgammaglobulinemia, possibly rendering the children more prone to URTI.

Clinical and immunological features in IgM deficiency.

BACKGROUND: IgM deficiency is a dysgammaglobulinemia characterized by isolated low levels of serum IgM. Patients with IgM deficiency may exhibit various clinical manifestations. However, IgM deficiency still remains to be explored with regard to diagnosis and treatment. METHODS: Through a retrospective chart review, we investigated the clinical and immunological features of 15 symptomatic adult IgM-deficient patients who were referred to our immunology clinics over a 4-year period. RESULTS: The patients were comprised of 6 males and 9 females, with a mean age of 57.2 years. On initial evaluation, 12 patients (80%) presented with susceptibility to infections, 5 (33%) had atopic manifestations such as asthma and allergic rhinitis, 3 (20%) had both infections and atopy, 4 patients (28%) had fibromyalgia-like symptoms, 3 (20%) had autoimmune manifestations, and 1 patient had lymphoma. The mean serum IgM level was 27.4 mg/dl (range 14-39). Impaired specific antibody response to pneumococcal antigens in 5 out of 11 studied patients (45%) appeared to be a notable association. Subtle abnormalities in IgG subclasses, lymphocyte subsets and in vitro proliferative lymphocyte responses were observed. Five patients who were treated with intravenous immunoglobulin responded very well. CONCLUSION: We propose that a thorough immunological evaluation including specific antibody responses be undertaken in patients with IgM deficiency. IgM-deficient patients who present with recurrent/severe infections may benefit from immunoglobulin treatment particularly in the presence of impaired pneumococcal antibody responses.

Chronic inflammatory demyelinating polyneuropathy associated with dysglobulinemia: a peripheral nerve biopsy study in 18 cases.

The possible occurrence of chronic inflammatory demyelinating polyneuropathy (CIDP) in association with an identified dysglobulinemic status is recognized and a causal relationship between the two has been suggested. We had the opportunity to study 18 patients presenting with CIDP and dysglobulinemia. This was an IgG monoclonal gammopathy (IgG MG) in 8 cases, an IgM monoclonal gammopathy (IgM MG) in 8, an IgG-IgM biclonal gammopathy in 1 case and an IgM monoclonal cryoglobulinemia in another. A peripheral nerve biopsy specimen was available for all patients and the morphological findings in these specimens in the cases of CIDP with IgG MG or cryoglobulin did not differ from those without, whereas characteristic features were observed in the cases of CIDP with IgM MG and anti-myelin associated glycoprotein activity.

[Selective IgA defect. Clinical importance for stomatology]. / Selektiver IgA-Defekt. Klinische Bedeutung in der Stomatologie.

The clinical picture of 6 women suffering from selective IgA immunodeficiency were studied in a 2-13 years lasting period of immunological outdoor patients care. Despite of respiratory infections, otitis media, sinusitis, aphtosis and exogenous allergy the first detection of IgA deficiency was delayed til adulthood (mean age 42 years). A case of a 22 years old women with complicated fistula after molar tooth extraction showed the problems of dentistry in such diagnosis. No significant deviation concerning periodontitis and caries has been demonstrated in all patients. However, the rate of IgA deficiency demands basic knowledge about diagnosis, prevention of local and systemic complications in this disease by all practising dentists.

Clinical and immunological evaluation of patients with selective IgA deficiency.

The clinical and immunological features of 14 patients including 12 with selective and two with partial IgA deficiency are presented. One patient was asymptomatic, six patients had allergic diseases, three patients had hematologic disorders and the remaining patients had chronic-recurrent infections. The IgG and IgM serum concentrations were high in four and two patients, respectively. Delayed hypersensitivity skin tests were applied to seven patients, and were found positive in all. E-rosette forming cells were within the normal range. In vitro lymphoblastic transformation with PHA was normal in all the patients, except for one. Two patients had no sIgA+ B cells. The percentage of CD+4 T cells was decreased in one patient and the percentage of CD+8 T cells was increased in another, both of whom had a low CD4/CD8 ratio. The heterogeneity of clinical and immunological features in these patients suggests that various mechanisms may be responsible for the immunopathogenesis of IgA deficiency.

Impaired lung function in patients with IgA deficiency and low levels of IgG2 or IgG3.

We examined the relation between serum levels of IgG subclasses and lung function, as determined by spirometry, lung volumes, the single-breath nitrogen test, and static recoil pressures, in 29 patients with IgA deficiency and repeated upper or lower respiratory tract infections. Four of the patients had decreased levels of IgG2, and two had decreased levels of IgG3. Two or more lung-function values were abnormal in each of these six patients and also in three others with normal levels of IgG subclasses. Low levels of IgG2 and IgG3 were significantly related to abnormal lung function (P less than 0.01). The 20 patients with normal lung function all had IgG-subclass levels above the lower range. There may be a causal relation between low levels of IgG subclasses and deterioration in lung function, suggesting that patients with combined IgA and IgG-subclass deficiencies may benefit from immunoglobulin prophylaxis.

Pathophysiologic analysis of peripheral blood lymphocytes from patients with primary immunodeficiency. I. Ig synthesis by peripheral blood lymphocytes stimulated with either pokeweed mitogen or Epstein-Barr virus in vitro.

In the present study 5 patients with common variable hypogammaglobulinemia (CVH) and 4 patients with selective IgA deficiency (IgA-D) were analyzed for the cellular defects responsible for impaired Ig synthesis with use of peripheral blood lymphocytes stimulated with either PWM or EBV in vitro. By the use of co-culture with PWM, all the patients examined had intrinsic B cell defects restricted to the synthesis of Ig class corresponding to the low or absent Ig class(es) in the sera. Two types of excessive suppressor T activity were found, which were abrogated by irradiation. One was isotype-nonspecific and the other was IgA-specific. Moreover, failure of IgA-specific helper T activity was demonstrated. The use of EBV as an agent that polyclonally activates B cells independently of T cells and monocytes should allow a clearer delineation of the level of the B cell defects. When co-cultured with EBV, B cells from 3 patients with CVH produced normal to subnormal quantities of IgM although they could produce no IgM upon co-culturing with normal T cells and PWM. B cells from 2 patients with CVH could produce IgM normally by stimulation with either PWM or EBV; however, there was no restoration to produce IgG or IgA in these patients. In addition, B cells from 2 patients with IgA-D produced not only IgG and IgM but also IgA almost normally at 4 days after in vitro stimulation with EBV.

Total selective deficiency of serum and secretory IgA associated with farmer's lung.

We present a case of total IgA deficiency associated with farmer's lung. The IgA deficiency is combined with the IgE one. IgA are absent both in the serum and in the bronchial secretions; they are present on the surface of B-lymphocytes, also after the enzymatic surface digestion and resynthesis test is performed. With intravenous perfusion of human gamma globulins, during repeated courses, IgA reach a normal level and exceed it, despite the IgA concentration in the perfused compound is very low and despite the fact that injected gamma globulins are not detectable with electrophoretic method. IgA never appear in the bronchial secretion. The association between both IgA and IgE deficiency, with this pulmonary disease, differential diagnostics, and therapeutical features, are discussed.

The clinical and physiological aspects of tuftsin deficiency syndromes exhibiting defective phagocytosis.

The tetrapeptide tuftsin (Thr-Lys-Pro-Arg) stimulates phagocytosis by blood neutrophilic granulocytes and tissue macrophages in a highly specific manner. Tuftsin is cleaved off the carrier gamma-globulin molecule as the free active form by two enzymes. One of these is in the spleen and the other on the outer membrane of the phagocyte. Congenital tuftsin deficiency usually arises when the peptide is mutated to an inactive peptide. The acquired type occurs if the spleen function is curtailed by removal or disease. Tuftsin deficiency is manifested by severe recurrent infections involving primarily the skin, lymph nodes and lungs. Therapy is limited to gamma-globulin injection along with appropriate chemotherapy.

The hypogammaglobulinemias.

The immunoglobulin system initially evolved as a defense system to maintain genetic stability during evolution. Studies in the past two decades have resulted in the elucidation of immunoglobulin structure and the definition of their chemical composition. Disorders of immunoglobulin production have led to an enhanced understanding of the functional aspects of immunoglobulin chemistry. The recognition of these disorders has enhanced our knowledge of antibody specificity and led to the development of immunochemical techniques such as radioimmunoassay as well as the development of techniques of transplantation and immune reconstitution in man.

The role of IgA in the prevention of bacterial colonization of the jejunum in the vagotomized subject.

The efficacy of three mechanisms of defence against jejunal bacterial colonization (i.e. gastric acid, vagal and pyloric integrity and intestinal IgA) has been investigated. Only in subjects with disturbance of all three mechanisms did significant jejunal colonization occur, and this was invariably associated with severe diarrhoea. Clearly normal intestinal IgA is of critical importance in the prevention of jejunal bacterial colonization in the vagotomized subject.