IGG SUBCLASSES IN THE LUNGS OF PATIENTS WITH INTERSTITIAL PNEUMONITIS FOLLOWING BONE-MARROW TRANSPLANTATION

Subclasses of immunoglobulin G (IgG) were measured in bronchoalveolar lavage (BAL) fluid and serum from rive normal volunteers and 25 bone marrow transplant (BMT) recipients, who developed 32 episodes of pneumonitis. Evidence for local production of the four subclasses was sought, to assess whether any observed deficiency was associated with any particular group of pulmonary infections. In the normal volunteers, IgG1 and IgG4 could be detected in BAL fluid from all subjects, with evidence for local production of IgG1 in one, and IgG4 in all five. IgG2 could be detected in BAL fluid from one subject, but IgG3 was undetectable in all normal BAL fluid. The BMT recipients differed from the normal volunteers mainly in the presence of IgG2 and IgG3 in BAL fluid. Furthermore, IgG4 could not be detected in BAL from seven. Furthermore, IgG4 could not be detected in BAL from seven episodes of pneumonitis (six patients). Bacteria, protozoa or fungi alone were isolated from five of these seven lavages, whereas pneumonitis associated with these organisms alone only occurred in 9 of the remaining 25 episodes of pneumonitis (19 patients) where there was also evidence for local production of IgG4. Moreover, 4 out of 7 patients with no detectable IgG4 in lavage developed secondary infections, whilst only 5 out of 19 patients producing IgG4 locally developed secondary infections (p=0.05). Although there was individual variation within each group, levels of local production of both IgG1 and IgG4 tended, however, to be higher in patients who died from pneumonitis than in those who recovered, suggesting that this may be a poor prognostic maker. These results suggest that IgG4 is an important immunoglobulin subclass in the lower respiratory tract, and may have a protective role against bacterial and fungal infections. Excessive local production of IgG1 and IgG4, however, could be associated with a poor prognosis.