We investigated the prevalence of virulent Rhodococcus equi in clinical isolates from 69 sporadic cases (60 men, 8 women, and 1 patient of unknown sex) in Chiang Mai, Thailand, between 1993 and 2001. Fifty were human immunodeficiency virus (HIV) positive, 3 were HIV negative, and HIV status was unknown for 16. Fifty-two (75%) of 69 isolates were strains of intermediate virulence that contained the virulence-associated 20-kDa antigen, and 17 isolates (25%) were avirulent. No virulent strains with the virulence-associated 15-17-kDa antigens were identified. R. equi was isolated from HIV-positive patients' houses and those of their neighbors: avirulent strains were widespread, but only 1 strain of intermediate virulence was isolated. R. equi strains of intermediate virulence were isolated from 4 (0.8%) of 500 submaxillary lymph nodes from apparently healthy pigs in Chiang Mai. The routes of R. equi acquisition should be investigated from the viewpoint of zoonosis and public health.
The plasmid types and serotypes of 164 Rhodococcus equi strains obtained from submaxillary lymph nodes of swine from different piggeries in 28 villages and towns located throughout the country were examined. The strains were tested by PCR for the presence of 15-to 17-kDa virulence-associated protein antigen (VapA) and 20-kDa virulence-associated protein antigen (VapB) genes. R. equi is an aerobic, gram-positive coccobacillus which frequently causes chronic suppurative bronchopneumonia with abscesses, lymphadenitis, and ulcerative enteritis in foals less than 6 months old (3,14). In addition to its virulence for foals, R. equi seems also to be an important pathogen to immunocompromised humans, such as organ transplant and AIDS patients (21). R. equi is also common in the submaxillary lymph nodes of pigs (2,8,15,25,27). Katsumi and others (8) isolated R. equi from 45.6% of the submaxillary lymph nodes of swine with lesions and from 9.4% of lymph nodes of swine without lesions. Takai and colleagues (19) described a 3.1% isolation rate on the basis of examination of 1,832 submaxillary lymph nodes collected from swine.Recently, the discovery of virulence-associated antigens and virulence plasmids has allowed classification of the virulence of More recently, we demonstrated that five of the seven clinical isolates of R. equi from immunocompromised patients expressed VapB and that they were of intermediate virulence and revealed that these human isolates contained a 95-kb type 5 plasmid which was also seen in the pig isolates in Hungary (10). The route of infection in human cases is not clear. The purpose of this study was to isolate virulent R. equi strains from submaxillary lymph nodes of swine in Hungary, to determine the genotypic diversity of virulence-associated plasmids found in them, and to examine the serotypes of the isolates with the aim of finding additional data to characterize the epidemiological relationship between human R. equi infections and pigs carrying R. equi in the submaxillary lymph nodes.Serotyping is a reliable method for examining R. equi strains. There are two systems for serotyping R. equi. Prescott de-* Corresponding author. Mailing address:
Objective
Coatomer subunit alpha (COPA) syndrome, also known as autoinflammatory interstitial lung, joint, and kidney disease, is caused by heterozygous mutations in COPA. We identified a novel COPA variant in 4 patients in one family. We undertook this study to elucidate whether and how the variant causes manifestations of COPA syndrome by studying these 4 patients and by analyzing results from a gene‐targeted mouse model.
Methods
We performed whole‐exome sequencing in 7 family members and measured the type I interferon (IFN) signature of the peripheral blood cells. We analyzed the effects of COPA variants in in vitro experiments and in Copa mutant mice that were generated.
Results
We identified a heterozygous variant of COPA (c.725T>G, p.Val242Gly) in the 4 affected members of the family. The IFN score was high in the members carrying the variant. In vitro analysis revealed that COPA V242G, as well as the previously reported disease‐causing variants, augmented stimulator of interferon genes (STING)–induced type I IFN promoter activities. CopaV242G/+ mice manifested interstitial lung disease and STING‐dependent elevation of IFN‐stimulated gene expression. In CopaV242G/+ dendritic cells, the STING pathway was not constitutively activated but was hyperactivated upon stimulation, leading to increased type I IFN production.
Conclusion
V242G, a novel COPA variant, was found in 4 patients from one family. In gene‐targeted mice with the V242G variant, interstitial lung disease was recapitulated and augmented responses of the STING pathway, leading to an increase in type I IFN production, were demonstrated.
Congenital self-healing Langerhans cell histiocytosis (CSHLCH) is a rare type of Langerhans cell histiocytosis (LCH). Here, we report two cases of CSHLCH. The cases presented solitary and multiple skin lesions of various sizes. The diagnosis was confirmed by skin biopsies. The lesions disappeared after one to two months without therapeutic intervention. No BRAF mutations in the skin lesions were detected, and soluble interleukin-2 receptor (sIL-2R) was normal in both cases. Recent studies suggested that the state of differentiation of the precursor cell in which BRAF mutations occur is associated with the clinical types and prognosis of the disease. Further investigation should be needed to elucidate the association between the progression and regression of CSHLCH and BRAF mutation.
COPA syndrome is an autoinflammatory disease with autoimmune and autoinflammatory manifestations affecting lungs, joints, and kidneys. COPA syndrome is caused by heterozygous loss-of-function mutations in the coatmer subunit alpha (COPA) gene, encoding α subunit of coatmer protein complex I (COP-I) coated vesicles. Mutant COPA induces constitutive activation of stimulator of interferon (IFN) genes (STING), leading to systemic inflammation and elevated type I interferon response. We have previously reported a Japanese family of COPA syndrome with a novel V242G mutation. Two out of 4 patients required lung transplantation due to intractable interstitial lung disease (ILD) and respiratory failure. Both of them deceased after lung transplantation, one due to sepsis and the other due to allograft dysfunction possibly caused by the reccurent ILD. The literature review indentified unfavorable outcome of the solid organ transplant in COPA syndrome and its related disease, however, precise clinico-pathological description of these cases has been scarce. Here, we report in detail the clinical course of our cases to clarify the pathophysiology of allograft dysfunction in COPA syndrome and propose potential therapeutic approaches to improve post-transplant graft survival.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.