Background/Purpose: Background: associations between autoimmune, immunodeficiency and hematological disorders are well known as well as with autoinflammatory conditions. Modern genetic testing allows to link these conditions not only clinically but on genetic level also.

Methods: literature review for possible connections between autoinflammatory and autoimmune disorder with myelodysplastic syndrome associated with SRP72 gene polymorphism.

Results: L., 3-year-old boy with past medical history of periodic fever, myelodysplastic syndrome (MDS) associated with pathologic polymorphism of gene SRP72 (C1384C T), multiple café au lait spots and autism spectrum disorder was admitted to our hospital due to fever. Fever episodes occurred since 6-month-old (up to 40C), every 3 months and lasted 5-15 days. The episodes associated with rash, conjunctivitis, arthralgias, reactive lymphadenopathy, oral and duodenal ulcers, Raynaud syndrome and elevation of C-reactive protein level during fever episodes. The initially managed the fever with Prednisone due to concerns for an autoimmune condition or PFAPA. The fever has improved to steroid in the early course of disorder but following episodes hasnt had any response. Extensive work up has been done. Autoimmune, immunology, oncology evaluation was negative, but genetic testing (microarray and Invitae primary immunodeficiency panel) was positive for pathologic polymorphism of gene SRP72. At 18-months of age, he was diagnosed with neutropenia first time. Family history was significant for periodic fever and lupus-like symptoms in his mother and rheumatoid arthritis in maternal uncle. Tests results were inconclusive for possible reason of his symptoms. Next comprehensive evaluation has been performed at National Institute of Health in June 2022. Full genome sequencing results are pending.

While definitive diagnosis is still not clear, we decided to look for possible links between MDS and his periodic fevers. In adults MDS associates with various autoimmune and autoinflammatory processes like vasculitis, inflammatory arthritis, autoimmune cytopenia. MDS associated with SRP72 polymorphism/mutation has familial involvement and usually early onset. The SRP72 is gene encoding one of the subunits of SRP (signal recognition particle) responsible for targeting of secretory protein to the endoplasmic reticulum (ER).

SRP72 cleaved during apoptosis possibly links to impaired tolerance to own peptides and self-autoantibodies formation that triggering the autoimmune diseases. Inappropriate protein production and degradation might be another non-immunologic mechanism triggering inflammation. Adequate function od ER and protein homeostasis are necessary for muscle tissue stability. There is association of SRP72 with idiopathic inflammatory myopathies (IIM). However, process of SRP72 synthesis and IIM in not fully known investigated. There are not know connections between MDS and periodic fever syndromes.

Conclusion: myelodysplastic syndrome associated with SRP72 gene polymorphism has strong association with IIM but not with autoinflammatory syndromes. Patient should have close monitoring for developing features of IIM

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/periodic-fever-syndrome-and-myelodysplastic-syndrome-possible-connections-between-two-disorders/