3 3 2 Editorial correspondence The Journal of Pediatrics August 1992

trol subjects might have been classified as case subjects. If we con- sider that breast-feeding among control subjects was significantly more frequent than among case subjects, the effect of such misclassification could have decreased the strength of the associa- tion that we have observed.

Alfredo Pisacane, MD Liberatore Graziano, AID

Gianfranco Mazzarella, MD Benedetto Scarpellino, AID

Gregorio Zona, MD Department of Pediatrics

Universitit di Napoli 80131 Napoli, Italy

IgG4 deficiency and recurrent respiratory infections To the Editor."

Moss et al. (J PEDIATR 1992;120:16-21) reported an increased incidence of IgG4 deficiency in children with recurrent respiratory tract infection. Several points should be considered in regard to the clinical significance of low levels of IgG4.

Among the four lgG subclasses, the role of IgG4 in the host de- fense mechanism is the least clear. Only IgG4 does not bind com- plement and has a low affinity to phagocytic cellsJ It has been sug- gested that IgG4 represents a non-IgE antibody that can sensitize basophils for the release of histamine, 2 but its exact role in allergy is still unknown.

Furthermore, one would expect that if IgG4 is important in re- current respiratory infection, its association with low IgG2, which has a more defined r01e in host defense, would lead to a marked in- crease in infection. Nevertheless, in the Moss study no significant increase was observed between the control subjects and the patients when both IgG2 and IgG4 levels were low.

The control group used by Moss et al. is a problematic one re- garding levels of IgG4. The control group was composed of 127 atopic children. Oxelius 3 showed increased levels of IgG4 in many atopic children, and this observation was confirmed by another in- vestigator. 4 Thus the small number of IgG4 deficient children in the control group may be misleading, and in the general population a higher incidence of children with low IgG4 may be found, similar to that observed in the recurrent respiratory infections group.

Further studies should be undertaken to clarify the clinical sig- nificance of low levels of IgG4 in children with recurrent respira- tory tract infection.

Amos Etzioni, MD Department of Pediatrics and Clinical Immunology

Rambam Medical Center B. Rappaport Faculty of Medicine

Technio~2 H. aifa 31096, Israel

R E F E R E N C E S

1. Schur PH. IgG subclasses: a review. Ann Allergy 1987;58:89- 99.

2. Vijay HM, Perelmutter L. Inhibition of reagin-mediated PCA reactions in monkeys and histamine release from human leu- kocytes by human IgG4 subclass. Int Arch Allergy Appl Im- munol 1977;53:78-85.

3. Oxelius VA. IgG subclasses and human disease. Am J Med 1984;76(4A):7-18.

4. Smith TF. Immunodeficiency in chronic pediatric respiratory illness. Hosp Pract 1986;21:143-58.

Reply To the Editor."

Dr. Etzioni correctly points out that we did not find a significant increase in infections in patients with multiple immunoglobulin isotype deficiencies (most commonly combined IgG2-IgG4 defi- ciency); only an increase in isolated IgG4 deficiency was found in the patients with recurrent infections. We mentioned in our article that our data in this respect resemble those previously reported by Heiner. 1 The mechanism for this apparent association is unex- plained; we welcome further studies attempting to corroborate our findings. Studies in this area, however, must use assays sufficiently specific and sensitive to yield accurate and informative data.

Studies of IgG2 deficiency suggest that isotype deficiencies may be markers of other immunodeficiency more proximal to clinical illness rather than direct causal factors. Thus, although compli- cated by the immunogenetic effect of allotype, 2, 3 sick IgG2-defi- cient individuals usually fail to mount adequate antibody responses to polysaccharide antigens, whereas healthy IgG2-deficient indi- viduals usually mount normal antibody responses. < 5 The problem that we found with isolated IgG4 deficiency was that the "stan- dard" battery of antibody responses to common protein and polysaccharide vaccine antigens identified antibody deficiencies in only a minority of our patients.

With regard to control populations, studies of atopic children have indicated that elevations of IgG4 may be more common than in healthy age-matched nonatopic individuals. However, this does not necessarily exclude an increase in IgG4-deficient individuals among atopic children compared with nonatopic children as well. 6

Richard Moss, AID Mary Ann Carmack, PhD, MD

Sylvia Esrig, BS Divisions of Allergy-Pulmonology and Infectious Disease

Department of Pediatrics Stanford University Medical Center

Palo Alto, CA 94304

R E F E R E N C E S

1. Heiner DC. lgG4 immunodefieiency. Allergy Proc 1988;9: 43-8.

2. Shackelford PG, Granoff DM, Nahm MH, et al. Relation of age, race, and allotypr to immunoglobulin subclass concentra- tions. Pediatr Res 1985;19:846-9.

3. Nahm MH, Macke K, Kwon O-H, et al. Immunologic and clinicar status of blood donors with subnormal levels of IgG2. J Allergy Clin Immunol 1990;85:769-77.

4. Shackelford PG, Granoff DM, Madassery JV, Scott MG, Nahm MH. Clinical and immunologic characteristics of healthy children with subnormal serum concentrations of IgG2. Pediatr Res 1990;27:16-21.

5. Shackelford PG, Granoff DM, Polmar SH, Scott MG, Gos- kowicz MC. Subnormal serum concentrations of IgG2 in chil- dren with frequent infections associated with varied patterns of immunologic dysfunction. J PEDIATR 1990; 116:529-38.

6. Heiner DC, Lee SI, Short JA. IgG4 subclass deficiency syn- dromes. Monogr Allergy 1986;20:149-56.