Figure 1.

Antigens of idiopathic pulmonary fibrosis (IPF). (A) Antigenicity of IPF lung explant extracts was greatest among the most acidic protein fractions (lowest pI). Proliferation was determined by bromodeoxyuridine (BrdU) incorporation among autologous hilar lymph node CD4 T cells (6). (B) Further fractionations of the acidic protein preparations by size filtration indicated the most immunogenetic antigens among the low pI proteins were greater than 50 kD. In these cases, proliferation was measured by ³H-thymidine because the preparations were limiting. (C) Prevalences of circulating anti–heat shock protein 70 (HSP70) IgG detected by immunoblots (IB) are depicted in healthy normal control subjects and patients with IPF. Respective subject numbers are denoted within columns. (D) HLA Class II DRβ1*11 alleles were underrepresented, whereas DRβ1*15 was overrepresented among the patients with IPF with anti-HSP70 autoantibodies. Prevalence is defined as the proportion of subjects with at least one allele copy. (E) Addition of rHSP70 to peripheral blood mononuclear cell cultures resulted in greater proliferation of CD4 T cells from patients with IPF, ascertained by BrdU incorporation, than in concurrent control cultures with no added antigens (Cnt), or cultures supplemented instead with glucose-regulated protein 78 (GRP78) (n = 24). Proliferation within GRP78-supplemented cultures did not significantly differ from those of control subjects. (F) IPF CD4 T cell IL-4 production was also more augmented by HSP70 than by the GRP78 (n = 15). The latter did not significantly differ from controls. CI = confidence interval; OR = odds ratio; SI = specific index.