Pulmonary Cladosporium infection coexisting with subcutaneous Corynespora cassiicola infection in a patient:A case report

BACKGROUND Cladosporium and Corynespora cassiicola(C.cassiicola)infections rarely occur in humans.Mutations in human caspase recruitment domain protein 9(CARD9)are reported to be associated with fungal diseases.Pulmonary Cladosporium infection coexisting with subcutaneous C.cassiicola infection in a patient with a CARD9 mutation has not been reported in the literature.CASE SUMMARY A 68-year-old male patient was hospitalized for hypertrophic erythema and deep ulcers on the left upper extremity.He was diagnosed with pneumonia caused by Cladosporium,as identified through bronchoalveolar lavage fluid analysis,and deep dermatophytosis caused by C.cassiicola,as identified through morphological characteristics of the wound secretion culture.He underwent antifungal therapy(voriconazole)and recovered successfully.He carried two mutations in CARD9(chr9:139266425 and chr9:139262240)and was therefore susceptible to fungal infections.CONCLUSION This case study is the first to report the coexistence of pulmonary Cladosporium infection and subcutaneous C.cassiicola infection in a patient with CARD9 mutation.Our findings will be helpful in enriching the phenotypic spectrum of fungal infections underlying CARD9 deficiency.

Interaction of the major inflammatory bowel disease susceptibility alleles in Crohn’s disease patients

AIM:To investigate the interaction of interleukin-23 receptor(IL23R)(rs1004819 and rs2201841),autophagy-related 16-like 1(ATG16L1)(rs2241880), caspase recruitment domain-containing protein 15 (CARD15)genes,and IBD5 locus in Crohn's disease(CD) patients. METHODS:A total of 315 unrelated subjects with CD and 314 healthy controls were genotyped.Interactions and specific genotype combinations of a total of eight variants were tested.The variants of IBD5locus(IGR2198a_1 rs11739135 and IGR2096a_1 rs12521868),CARD15(R702W rs2066845 and L1007fs rs2066847),ATG16L1(rs2241880)and IL23R (rs1004819,rs2201841)genes were genotyped by PCR-RFLP,the G908R(rs2066844)in CARD15 was determined by direct sequencing. RESULTS:The association of ATG16L1 T300A with CD was confirmed[P=0.004,odds ratio(OR)=1.69, 95%CI:1.19-2.41],and both IL23R variants were found to represent significant risk for the disease(P= 0.008,OR=2.05,95%CI:1.20-3.50 for rs1004819 AA;P<0.001,OR=2.97,95%CI:1.65-5.33 for rs2201841 CC).Logistic regression analysis of pairwise interaction of the inflammatory bowel disease (IBD)loci indicated that IL23R,ATG16L1,CARD15 and IBD5(IGR2198a_1)contribute independently to disease risk.We also analysed the specific combina- tions by pair of individual ATG16L1,IL23R rs1004819, rs2201841,IGR2198a_1,IGR2096a_1 and CARD15 genotypes for disease risk influence.In almost all cases,the combined risk of susceptibility pairs was higher in patients carrying two different risk-associated gene variants together than individuals with just one polymorphism.The highest OR was found for IL23R rs2201841 homozygous genotype with combination of positive CARD15 status(P<0.001,OR=9.15,95% CI:2.05-40.74). CONCLUSION:The present study suggests a cumulative effect of individual IBD susceptibility loci.

The Role of CARD9 in Metabolic Diseases

Caspase recruitment domain containing protein 9(CARD9)is an adaptor protein that plays a critical role in pattern recognition receptors(PRRs)-mediated activation of NF-kB and mitogen-activated protein kinase(MAPK).This elicits initiation of the pro・inflammatory cytokines and leads to inflammatory responses,which has been recognized as a critical contributor to chronic inflammation.Current researches demonstrate that CARD9 is strongly associated with metabolic diseases,such as obesity,insulin resistance,atherosclerosis and so on.In this review,we summarize CARD9 signaling pathway and the role of CARD9 in metabolic diseases.