Pregnancy probabilistically augments potential precursors to chronic, immune-mediated or autoimmune lacrimal gland infiltrates

Abstract Purpose This study asked whether pregnancy, a risk factor for dry eye disease associated with both chronic, immune-mediated- and autoimmune etiologies, augments development of clusters of coordinately functioning cells (CCFC) that may be precursors to pathological lacrimal gland infiltrates. Methods Lacrimal glands were from six virgin- and six term-pregnant rabbits of the same age and environmental exposure history. Seventy-two immune response-related gene transcripts were assayed by real time RT-PCR. Principal component (PC) analysis identified transcript signatures of CCFC contributing negative ( ⊖ ) or positive ( ⊕ ) PC loadings and determined gland PC projections, which reflect levels of CCFC development. Results Three CCFC were of interest as potential precursors to pathological infiltrates. CCFC 1 ⊖ was suggestive of an ectopic lymphoid structure with resting T cells and B cells. CCFC 1 ⊕ was suggestive of an immune-mediated infiltrate with T H 1 cells and mature, cytotoxic B cells. CCFC 2 ⊖ was suggestive of an ectopic lymphoid structure with activated T cells, mature B cells, germinal center, and plasmacytes. CCFC 4 ⊖ and CCFC 5 ⊖ also included plasmacytes. Pregnancy augmented CCFC 1 ⊖ in some glands; augmented CCFC 1 ⊕ in others; and augmented CCFC 2 ⊖ , CCFC 4 ⊖ , and CCFC 5 ⊖ different combinations. Conclusions Potential precursors of pathological infiltrates form in the lacrimal glands by the time of sexual maturity. Pregnancy augments lacrimal gland plasmacyte populations, and it can augment development of potential precursors to either chronic, immune-mediated infiltrates or autoimmune infiltrates of various phenotypes. Systemic and strictly local, probabilistic phenomena interact with pregnancy to determine which combinatorial phenotypes are favored.