Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Microchimerism (Mc), harboring a small number of cells (or DNA) that originated in a different individual, occurs commonly due to bi-directional maternal-fetal exchange during pregnancy and long-term persistence decades later. Mc has been implicated in some autoimmune diseases, especially systemic sclerosis (SSc), but any role in pathogenesis remains unclear. We sought to identify and characterize Mc at the site of disease pathology in SSc lung.
Patients and Methods:
SSc lung specimens were obtained from autopsy. Of 9 patients, 7 had diffuse and 2 limited SSc; 6 were female, 3 male. SSc onset age ranged from 25 to 56 (mean 45.6) and disease duration 1 to 8 years (mean 3.1). Causes of death were primarily pulmonary (interstitial fibrosis, hemorrhage), however 3 patients had cancer (1 lung, 2 breast) and cause of death was unclear for 1 patient. 3 had undergone autologous hematopoietic cell transplants and 2 cord blood transplants. For comparison, healthy tissue from surgical lung cancer resections are being studied, to date 2 females and 2 males.
To identify and characterize Mc, two approaches were employed. When family members were available, a non-shared polymorphism of the putative Mc source was identified and DNA extracted from lung tissue interrogated for the specific polymorphism by quantitative-polymerase chain reaction (qPCR). When the Mc source was sex mismatched, fluorescence in situ hybridization (FISH) was employed with X- and Y-chromosome specific probes. Concomitant immunohistochemistry (IHC) was added for CD31, CD45, cytokeratin and SMA-α to determine cell phenotype. Cells with two distinct signals within one nucleus were counted and analyzed under bright field for IHC staining.
Results: Molecular studies indicated multiple Mc sources are detected in SSc lung, i.e. maternal, fetal and possibly sibling Mc. By polymorphism specific qPCR concentrations ranged from 1 to 144 microchimeric cell equivalents per 105 cell tested. By FISH 3/3 male lungs had female cells (mean: 9.3/2000, range 3-19) and 4/5 female lungs had male cells (mean: 5.8/2000, range 1-13). Among controls, 3/4 had Mc (mean: 5/2000, range 1-8). Interestingly, in male SSc patients, half or more of maternal Mc was positive for the endothelial cell marker CD31. 10% were positive for SMA-α. In females, 36% of the male Mc was positive for CD31, 9.5% for SMA-α and 3.5% for cytokeratin. No microchimeric cell was positive for CD45.
These results indicate SSc lung contains Mc from multiple different sources. Microchimeric cells in the lung were not hematopoietic. The most common phenotype was endothelial, of potential additional interest in light of early endothelial cell injury in SSc. While other studies are needed, these results, along with other literature, 1 indicate that Mc can adopt different cell phenotypes so that loss of tolerance to our natural immigrants could contribute to an “auto” immune disease.
Acknowledgements: This work was supported by a grant from the Scleroderma Foundation.
1 Reviewed in: Nelson JL. The Otherness of Self: Microchimerism in health and disease. Trends in Immunol 33(8):421-7, 2012.
To cite this abstract in AMA style:GENTIL C, Randolph-Habecker J, Madtes DK, FANG M, Gammill HS, Fligner CL, Houghton MA, Nelson JL. Microchimerism Is Present in Systemic Sclerosis Lung and Includes CD31-Positive Cells [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/microchimerism-is-present-in-systemic-sclerosis-lung-and-includes-cd31-positive-cells/. Accessed October 18, 2019.
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