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Objective: This study aimed to assess the disease conditions of patients with inflammatory bowel disease (IBD) in Hubei Province during the outbreak of Coronavirus Disease 2019 (COVID-19) by questionnaire online and guide their self-management during this epidemic. Results: A total of 102 eligible questionnaires were included. No patient we surveyed reported a diagnosis of COVID-19. Our result showed that 67.86% of patients with ulcerative colitis (UC) and 80.43% of patients with Crohn's disease (CD) were in remission, 85.29%of patients had a good quality of life. Part of the patients (21.57%) reported their disease conditions worsening. The reduction in physical exercise was a risk factor for worsening conditions (OR=17.593, p=0.009). Some patients reported an alteration of medication regimens during the epidemic. Conclusions: The epidemic of COVID-19 might have a certain impact on many aspects of Hubei IBD patients within four weeks after the traffic control. Doctors could utilize the results from our questionnaire to guide IBD patients’ self-management. Methods: A questionnaire was designed containing the Harvey-Bradshaw Index (HBI), the 6-point Mayo Score, the short inflammatory bowel disease questionnaire (SIBDQ) and distributed to Hubei IBD patients online within four weeks of traffic control after the outbreak, it also included questions about patients’ self-reported disease conditions and their epidemiological features of COVID-19.

Interferon regulatory factor 4 (IRF4) is a transcription factor (TF) and key regulator of immune cell development and function. We report a recurrent heterozygous mutation in IRF4, p.T95R, causing an autosomal dominant combined immunodeficiency (CID) in seven patients from six unrelated families. The patients exhibited profound susceptibility to opportunistic infections, notably Pneumocystis jirovecii , and presented with agammaglobulinemia. Patients’ B cells showed impaired maturation, decreased immunoglobulin isotype switching, and defective plasma cell differentiation, whereas their T cells contained reduced T H 17 and T FH populations and exhibited decreased cytokine production. A knock-in mouse model of heterozygous T95R showed a severe defect in antibody production both at the steady state and after immunization with different types of antigens, consistent with the CID observed in these patients. The IRF4 T95R variant maps to the TF’s DNA binding domain, alters its canonical DNA binding specificities, and results in a simultaneous multimorphic combination of loss, gain, and new functions for IRF4. IRF4 T95R behaved as a gain-of-function hypermorph by binding to DNA with higher affinity than IRF4 WT . Despite this increased affinity for DNA, the transcriptional activity on IRF4 canonical genes was reduced, showcasing a hypomorphic activity of IRF4 T95R . Simultaneously, IRF4 T95R functions as a neomorph by binding to noncanonical DNA sites to alter the gene expression profile, including the transcription of genes exclusively induced by IRF4 T95R but not by IRF4 WT . This previously undescribed multimorphic IRF4 pathophysiology disrupts normal lymphocyte biology, causing human disease.

Background Systemic autoinflammatory diseases (SAIDs) are hyperinflammatory and immune-dysregulation conditions that present in childhood. This kind of disease is a rare disease with early-onset, severe condition and difficult diagnosis, which seriously affects the growth and development of children. Most children need a genetic diagnosis. However, with the limitation of access to genetic testing and the detection of somatic mutations, the diagnosis of SAIDs remains challenging. IL-1 is one of the important cytokines involved in the pathogenesis of SAIDs. Here we briefly review monogenic SAIDs mediated by aberrant IL-1 production, with the aim to further understand the pathogenesis, clinical manifestations and treatments of IL-1 mediated SAIDs. Methods Literature reviews were performed using “PubMed” and “Web of Science” by searching for the terms “autoinflammatory diseases” and “IL-1”. Results Monogenic SAIDs mediated by IL-1 include MKD, FMF, TRAPS, PAAND, PAPA, CAPS, DIRA, Majeed syndrome, NAIAD, NLRC4-MAS, PFIT, APLAID. Monogenic SAIDs have early onset, various clinical manifestations and difficult diagnosis, so early recognition and early treatment can reduce the complications and enhance the quality of life. Conclusions There are many kinds of IL-1 mediated SAIDs. Pediatricians should be alert to SAIDs in the face of the patients with repeated fever, repeated rash and poor effect of routine treatment. The patients should be carried out with gene testing and treatment in time.