Background: There are four members in NLR family, NLRP3, NLRC4, NLRP1, and NLRP12, the mutations of which can lead to autoinflammatory diseases, while little reports describe those diseases in Chinese population.

Objectives: To report several cases of NLR-related autoinflammatory diseases in our center and to compare the differences of the presentations of CAPS between Chinese and western patients.

Methods: This study was undertaken at Peking Union Medical College Hospital (PUMCH) between 2012 and 2019. Demographic data, clinical presentations and genetic results were collected.

Results: 15 patients had been diagnosed as NLR-related autoinflammatory diseases in our center, including 11 CAPS, 1 FCAS4 and 3 NLRP12-AD patients.

We found 10 NLRP3 mutations, 3 NLRP12 mutations and 1 NLRC4 mutation. There are 3 novel mutations: NLRP3 c.1311G>T, NLRP3 c.1711G>A, and NLRC4 c.514G>A.

The major symptoms of those diseases are similar, such as recurrent episodes of fever associated with rash. And some may suffer from arthritis/arthralgia, uveitis, sensorineural deafness, symptoms of central neural systems (CNS).

On the other hand, different inflammasomopathies have unique characteristics. Symptoms of FCAS1, the mildest CAPS disorder, including rash and fever with/without arthritis/arthralgia, usually develop in the first year of life. The onset age of MWS is later (8m to 5y), and those patients were more likely to develop arthritis/arthralgia, eye involvement, hearing loss and symptoms of CNS. NOMID was the most severe type, and was presented with chronic urticarial-like rash shortly after birth, as well as severe CNS manifestations and musculoskeletal involvement. One of our NOMID patients had clubbing fingers, which was not reported before. The onset age of NLRP12-AD ranges from 6m to 5y and the presentation is similar to MWS while the FCAS4 patient presented with rash and fever, like FCAS1.

For laboratory examinations, all patients had raised inflammatory markers like ESR or CRP. Most of those patients had increased cytokines, including IL-1β, IL-6 as well as TNF-α. Leukocytosis and thrombocytosis were also observed in most patients, while anemia was mostly found in patients diagnosed as NOMID.

We also compared the clinical manifestations of CAPS between Chinese and western patients. The frequency of fever in Chinese is much higher than that in western population, while less Chinese patients suffered from ocular manifestations. Besides, Chinese patients seem to exhibit higher frequencies of severe symptoms, either CNS symptoms, or musculoskeletal symptoms, albeit with insignificant difference.

Conclusion: We reported a case series of NLR-related autoinflammatory disease and found some novel mutated alleles and clinical phenotypes, which expanded our knowledge to those diseases. By comparing clinical manifestations of CAPS patients in China and in western countries, it seems that the symptoms in different populations are not identical.

REFERENCES:

[1]Levy R, Gerard L, Kuemmerle-Deschner J, Lachmann HJ, Kone-Paut I, Cantarini L et al. Phenotypic and genotypic characteristics of cryopyrin-associated periodic syndrome: a series of 136 patients from the Eurofever Registry. Ann Rheum Dis. 2015;74(11):2043-9.

[2]Li C, Tan X, Zhang J, Li S, Mo W, Han T et al. Gene mutations and clinical phenotypes in 15 Chinese children with cryopyrin-associated periodic syndrome (CAPS). Sci China Life Sci. 2017;60(12):1436-44.

Acknowledgments: We’d like to thank the patients as well as their parents for their participation.

Disclosure of Interests: None declared