Decline of antibodies in XLA infant: when to start IVIG.

Patients with X-linked agammaglobulinemia (XLA) are protected for the first few months of life by maternal antibody, which is actively transported across the placenta during the last months of pregnancy (1). Patients do not typically present clinically with infection until after 6 months of age, when the infant’s maternally derived antibody level approaches zero (2). After the diagnosis, treatment includes replacement intravenous immunoglobulin (IVIG), which significantly reduces the risk of infection (3). The rate of decline for specific maternal antibody loss has not been well studied in patients with XLA that are followed from birth, even in patients with a positive family history. Information on the decline of specific maternal antibodies may be important in deciding when to start immunoglobulin replacement in these cases, apart from just knowing the serum IgG level. We had the unusual opportunity to study specific maternal antibody decay in a full-term (39 week gestation) male infant with a BTK mutation (161delG) diagnosed prenatally with a frameshift with amino acid changes in codons 54 and 55 and a termination codon in position 56. The baby’s serum IgG level was within normal limits for age at birth: 890 mg/dl (Table 1). When the child was brought to Texas Children’s Hospital at 2 months of age, his IgG level had dropped to 393 mg/dl (normal), and his IgA and IgM levels were detectable. As measured at 2 months of life, the patient had serological evidence of transplacental specific maternal antibody with wide diversity to diphtheria toxoid: 0.57 IU/ml (>0.1 IU/ml protective), tetanus toxoid: 2.15 IU/ml (>0.1 IU/ml protective), Haemophilus influenzae type b: 1.3 lg/ml (>1.0 lg/ml protective), and 1/4 positive serotypes of pneumococcus tested in the mother 2 months postpartum (serotype 7F:4.21 lg/ml, >1.3 lg/ml protective (Table 1). Values of optimal protective levels of these antibodies were assumed from information given by the testing laboratories and clinical experience. Lymphocyte phenotyping performed at 2 months of age confirmed the expected results: absent B cells (0.2% CD20 cells, 6 CD20cells/ll (when compared to normal ranges 6–28%, 256–1579 cells/ll). Lymphocyte proliferation studies with mitogens and antigens were normal (data not shown). At 3 months of age, the baby’s serum IgG level dropped to 254 mg/dl (normal) Maternal antibody levels in XLA neonates may predict when to start replacement IgG. ALLERGY Net