2020 Pediatric Rheumatology Research in Review

Dr. von Scheven also presented a group of papers addressing healthcare disparities in pediatric rheumatology patients, including a study by Rubinstein et al. on disparities in childhood-onset lupus that reported Black children with end-stage renal disease are half as likely to receive renal transplants as white children and almost twice as likely to die.¹⁴ She reiterated the words of the authors that “some patients remain largely invisible in the literature,” and stressed that this is a call to action, with more studies on health disparities in pediatric rheumatology desperately needed.

Basic & Translational Research

In his presentation, Dr. Schulert focused on basic and translational pediatric rheumatology research. He said COVID-19 was a dominating trend in research, with a PubMed search revealing 433 articles on JIA and 3,851 articles on pediatric COVID-19. One of these papers he described, by Consiglio et al., addressed SARS CoV-2-associated MIS-C immunology. The investigators found a distinct, overall serum inflammatory profile in MIS-C that differed from severe acute COVID-19 and Kawasaki disease, and included uniquely elevated interleukin (IL) 17α.¹⁵

Dr. Schulert

Dr. Schulert highlighted several other publications he found significant in 2020 that have the potential to change the way pediatric rheumatologists think about and treat pediatric rheumatic diseases going forward. These fall into six themes: pyrin, familial Mediterranean fever (FMF) and the plague; ENCODE: Encyclopedia of DNA Elements; molecular heterogeneity of pediatric lupus; pre-inflammatory mesenchymal (PRIME) cells; genetics of PFAPA; and dissecting the interferon (IFN) signature.

Considering the current pandemic and covering the topics of pyrin, FMF and the plague, he highlighted a study by Park et al. on ancient FMF mutations in human pyrin and resistance to Yersinia pestis (the Black Plague).¹⁶ FMF is caused by recessively inherited mutations in the MEFV gene, encoding the pyrin inflammasome. Because heterozygous carrier frequencies are very high in some Mediterranean populations, it has been suggested this is a selective advantage involving resistance to Yersinia pestis infection. By studying historical data, the researchers found Yersinia pestis mutations rapidly increased around Black Plague epidemics, and that Yersinia virulence factor YopM inhibits pyrin inflammasome formation and YopM binding to pyrin substantially reduced FMF mutation pyrin. Dr. Schulert said these findings together suggest an evolutionary and functional link between the prototypical FMF variant pyrin autoimmune disease with one of the most important pathogens in human history.

Moving from microbiology to “the biggest of big data,” Dr. Schulert described several papers on ENCODE: Encyclopedia of DNA Elements. Van Nostrand et al. introduced a large dataset of RNA elements that are bound by RNA-binding proteins (RBP) across the genome and identified RBP binding sites on RNA and chromatin in vivo, which provides “an incredible resource for our emerging understanding of genomics in rheumatic diseases,” he said.¹⁷