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489 IgG subclass abnormalities and antibody (AB) responses to tetanus toxoid (TT) in children with seizure disorders
487
488
ASSOCIATION OF SINOPULMONARY DISEASE AND SELECTIVE ANTI-H.INFLUENZAE B POLYSACCHARIDE DEFICIENCY IN CHILDREN. K.C. Eisermann-Rogers, M.N. Morris and S.H. Polmar, St. Louis, MO. Recurrent sinopulmonary infections have been reported in children with IgG2 subclass deficiency and inability to synthesize antibodies (Ab) to Hemophilus influenzae type b polysaccharide (Hib-PS). We studied 5 children (2.5-6yrs) with persistent sinopulmonary infections who had normal(n1) serum immunoglobulin isotype and IgG subclass levels but were unable to synthesize Ab to Hib-PS. All patients(pts.) had chronic sinusitis and chronic otitis media; 2/5 had recurrent lower respiratory tract infections. All pts. had nl blood lymphocyte population and subpopulation studies as well as nl proliferative responses to mitogens and antigens and nl delayed hypersensiAll showed poor Ab responses tivity skin tests. to Hib vaccine, even after repeated immunization. Three of 5 had nonprotective Ab titers to tetanus toxoid after routine immunization but had an adequate response after DT reimmunization. Nl antipneumococcal Ab titers were found in 4/4 pts. In vitro IgG and IgM synthesis by pokeweed mitogen stimulated lymphocytes revealed T-helper!inducer dysfunction in 2/5 and excessive T-suppressor cell activity in 2 pts. One pt. with T-helper/ inducer dysfunction developed an intrinsic B-cell defect after 1 yr. A pt. with excessive Tsuppressor activity developed panhypogammaglobulinemia over the course of 2 yrs. Prognosis for pts. with selective Hib-PS Ab deficiency is unclear. Serial studies of the type described above may be helpful in predicting pt. outcome and in understanding the immunopathological mechanisms involved.
489
ISOLATED IgM ANTI-POLYSACCHARIDE DEFICIENCY S.L. Andrew, M.D. and D.P. Huston, M.D. Houston, TX The mechanism underlying an isolated IgM deficiency in a 60 year old woman was investigated. The serum IgM was persistently low at 16 mg/dl (normal 60-300 mg/dl). Serum IgG, IgG subclasses, and IgA levels were normal. Delayed type hypersensitivity skin test responses were intact. Phenotyping of the patient’s peripheral blood mononuclear cells (PBMC) revealed normal numbers of T cell subsets and B cells. Surface IgM was present on B cells. PBMC were cultured with pokeweed mitogen or Staphylococcus aureus Cowan I. After 10 days, Ig in the culture supernatants was measured by isotypespecific ELISA. Both mitogens stimulated IgG, IgA and IgM production equivalent to that of normal controls. Cell mixing studies using E-rosette positive and E-rosette negative PBMC from the patient and normal controls further demonstrated the patient to have normal T helper cell function and lack of excessive T suppressor cell activity for all Ig isotypes. The patient and normal controls were immunized with tetanus toxoid (TT) and pneumococcal polysaccharide (PPS). vaccines. ELISAs were used to detect antigen specific serum antibody titers prior to and following immunizations. After immunization, the patient had normal amounts of IgM and IgG anti-IT antibodies and IgG anti-PPS antibodies. Anti-TT IgG responses were predominantly of the IgG1 subclass while the anti-PPS responses were predominantly of the IgG2 subclass. However, in contrast to normals, the patient did not mount an IgM antibody response to PPS. In addition, the serum contained IgG but no IgM isohemagglutinins. This is the first report of an isolated IgM antipolysaccharide immunodeficiency.
490
IgG SUBCLASS ABNORMALITIES AND ANTIBODY (AB) RESPONSES TO TETANUS TOXOID (TT) IN CHILDREN WITH SEIZURE DISORDERS. B. Kornbrot, MD: M.L. Weil. MD; and D.C. Heiner. MD.PhD. Torrance, CA. It has been suggested that immune mechanisms may play a role in childhood epilepsy. We have studied 65 patients, age 9 months to 19 years, with seizure disorders. Serum IgG subclass levels were measured, as well as AB to TT. Total IgGl, IgG2, and IgG3 were per-
formed
by radial
and AB levels
to
immunodiffusion.
IgG4
TT were
by
measured
solid phase radioimmunoassay. 21 patients (32.3%) had one or more abnormally low IgG subclass levels (less than 8-2SD) in comparison with agerelated normals: il patients had-low IgG2, 9 had low IgG4 and one had a low IgGl level. 28 (43.1%) had an abnormally high IgG subclass level: 17 patients had high IgGl, 10 high IgG4, and 1 a high IgG2 level. The AB response to TT in the study group (geometric mean 4.78 ug/ml) was significantly lower than that of agematched healthy controls (geometric mean 7.22 ug/ml, P10.007.) IgG subclass deficiencies were described by Duse et al, in a small group of seizure patients, most of whom had good clinical response to intravenous immunoglobulins. Our data provide additional evidence of IgG subclass abnormalities
in
hood seizures
290
children
taking
with
chronic
child-
anticonvulsants.
DouBLE-BLIND,PLxl3Eo-aJ@JTRorJzDTRIz&0FHEPP~ (IgE -DE) FOR INJECTION. GS Hahn, MD, RI? Rangus, and D Holmes, PhD, San Diego, CA. The treatment of seasonal allergic rhinitis with HEPPTM (IgE pentapeptide) for Injection was studied in this 51 patient, single center, double-blind, placebo-controlled trial. Thirty-five males and 16 females were randomly assigned to either HEPPTM or placebo treatment. Following a one-week baseline evaluation, 33 patients received HEPPTM 20 mg and 18 received placebo S.C. injections twice weekly for 6 weeks. Comparison of intake and outtake nhvsic--z-cal exams and laboratory tests demonstrated the safety of HEPPTM for Injection. Two HEPPTM patients reported minor-adverse effects. Daily diaries of 9 symptoms were maintained by each patient. The HEPPTM group demonstrated significantly more improvement for sneezing (p
488
ASSOCIATION OF SINOPULMONARY DISEASE AND SELECTIVE ANTI-H.INFLUENZAE B POLYSACCHARIDE DEFICIENCY IN CHILDREN. K.C. Eisermann-Rogers, M.N. Morris and S.H. Polmar, St. Louis, MO. Recurrent sinopulmonary infections have been reported in children with IgG2 subclass deficiency and inability to synthesize antibodies (Ab) to Hemophilus influenzae type b polysaccharide (Hib-PS). We studied 5 children (2.5-6yrs) with persistent sinopulmonary infections who had normal(n1) serum immunoglobulin isotype and IgG subclass levels but were unable to synthesize Ab to Hib-PS. All patients(pts.) had chronic sinusitis and chronic otitis media; 2/5 had recurrent lower respiratory tract infections. All pts. had nl blood lymphocyte population and subpopulation studies as well as nl proliferative responses to mitogens and antigens and nl delayed hypersensiAll showed poor Ab responses tivity skin tests. to Hib vaccine, even after repeated immunization. Three of 5 had nonprotective Ab titers to tetanus toxoid after routine immunization but had an adequate response after DT reimmunization. Nl antipneumococcal Ab titers were found in 4/4 pts. In vitro IgG and IgM synthesis by pokeweed mitogen stimulated lymphocytes revealed T-helper!inducer dysfunction in 2/5 and excessive T-suppressor cell activity in 2 pts. One pt. with T-helper/ inducer dysfunction developed an intrinsic B-cell defect after 1 yr. A pt. with excessive Tsuppressor activity developed panhypogammaglobulinemia over the course of 2 yrs. Prognosis for pts. with selective Hib-PS Ab deficiency is unclear. Serial studies of the type described above may be helpful in predicting pt. outcome and in understanding the immunopathological mechanisms involved.
489
ISOLATED IgM ANTI-POLYSACCHARIDE DEFICIENCY S.L. Andrew, M.D. and D.P. Huston, M.D. Houston, TX The mechanism underlying an isolated IgM deficiency in a 60 year old woman was investigated. The serum IgM was persistently low at 16 mg/dl (normal 60-300 mg/dl). Serum IgG, IgG subclasses, and IgA levels were normal. Delayed type hypersensitivity skin test responses were intact. Phenotyping of the patient’s peripheral blood mononuclear cells (PBMC) revealed normal numbers of T cell subsets and B cells. Surface IgM was present on B cells. PBMC were cultured with pokeweed mitogen or Staphylococcus aureus Cowan I. After 10 days, Ig in the culture supernatants was measured by isotypespecific ELISA. Both mitogens stimulated IgG, IgA and IgM production equivalent to that of normal controls. Cell mixing studies using E-rosette positive and E-rosette negative PBMC from the patient and normal controls further demonstrated the patient to have normal T helper cell function and lack of excessive T suppressor cell activity for all Ig isotypes. The patient and normal controls were immunized with tetanus toxoid (TT) and pneumococcal polysaccharide (PPS). vaccines. ELISAs were used to detect antigen specific serum antibody titers prior to and following immunizations. After immunization, the patient had normal amounts of IgM and IgG anti-IT antibodies and IgG anti-PPS antibodies. Anti-TT IgG responses were predominantly of the IgG1 subclass while the anti-PPS responses were predominantly of the IgG2 subclass. However, in contrast to normals, the patient did not mount an IgM antibody response to PPS. In addition, the serum contained IgG but no IgM isohemagglutinins. This is the first report of an isolated IgM antipolysaccharide immunodeficiency.
490
IgG SUBCLASS ABNORMALITIES AND ANTIBODY (AB) RESPONSES TO TETANUS TOXOID (TT) IN CHILDREN WITH SEIZURE DISORDERS. B. Kornbrot, MD: M.L. Weil. MD; and D.C. Heiner. MD.PhD. Torrance, CA. It has been suggested that immune mechanisms may play a role in childhood epilepsy. We have studied 65 patients, age 9 months to 19 years, with seizure disorders. Serum IgG subclass levels were measured, as well as AB to TT. Total IgGl, IgG2, and IgG3 were per-
formed
by radial
and AB levels
to
immunodiffusion.
IgG4
TT were
by
measured
solid phase radioimmunoassay. 21 patients (32.3%) had one or more abnormally low IgG subclass levels (less than 8-2SD) in comparison with agerelated normals: il patients had-low IgG2, 9 had low IgG4 and one had a low IgGl level. 28 (43.1%) had an abnormally high IgG subclass level: 17 patients had high IgGl, 10 high IgG4, and 1 a high IgG2 level. The AB response to TT in the study group (geometric mean 4.78 ug/ml) was significantly lower than that of agematched healthy controls (geometric mean 7.22 ug/ml, P10.007.) IgG subclass deficiencies were described by Duse et al, in a small group of seizure patients, most of whom had good clinical response to intravenous immunoglobulins. Our data provide additional evidence of IgG subclass abnormalities
in
hood seizures
290
children
taking
with
chronic
child-
anticonvulsants.
DouBLE-BLIND,PLxl3Eo-aJ@JTRorJzDTRIz&0FHEPP~ (IgE -DE) FOR INJECTION. GS Hahn, MD, RI? Rangus, and D Holmes, PhD, San Diego, CA. The treatment of seasonal allergic rhinitis with HEPPTM (IgE pentapeptide) for Injection was studied in this 51 patient, single center, double-blind, placebo-controlled trial. Thirty-five males and 16 females were randomly assigned to either HEPPTM or placebo treatment. Following a one-week baseline evaluation, 33 patients received HEPPTM 20 mg and 18 received placebo S.C. injections twice weekly for 6 weeks. Comparison of intake and outtake nhvsic--z-cal exams and laboratory tests demonstrated the safety of HEPPTM for Injection. Two HEPPTM patients reported minor-adverse effects. Daily diaries of 9 symptoms were maintained by each patient. The HEPPTM group demonstrated significantly more improvement for sneezing (p