Human herpesvirus 8 infection

A new study confirms that idiopathic plasmacytic lymphadenopathy is an independent disease subtype of idiopathic multicentric Castleman disease. Idiopathic plasmacytic lymphadenopathy (IPL) is a clinical condition marked by an excessive amount of antibody production due to the proliferation of polyclonal plasma cells in the lymph nodes. At present, it is not clear if IPL is a subtype of idiopathic multicentric Castleman disease (iMCD)-not otherwise specified (NOS). In a new study, researchers from Okayama University have found clinicopathological evidence needed to establish a separate disease unit for IPL under iMCD-NOS. Multicentric Castleman disease (MCD) comprises a heterogenous group of rare disorders that exhibit generalized symptoms such as swelling of lymph nodes, anemia, fever, and fatigue. The causative factors underlying MCD include Kaposi sarcoma-associated herpesvirus (KSHV)/ human herpesvirus 8 (HHV8) infections. KSHV/HHV8-negative MCD without association with the POEMS (polyneuropathy, organomegaly, endocrinopathy, M proteins, and skin changes) syndrome are termed "idiopathic," i.e., diseases with no identifiable cause, and are thus referred to as "iMCD." At present, specific clinical manifestations or diagnostic criteria have not been identified for iMCD, which often results in treatment delay. iMCD is further classified as iMCD-TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly) and iMCD-NOS (not otherwise specified). With additional research efforts, iMCD-NOS, which is highly heterogenous, could be classified into various subtypes. Interestingly, a disease known as idiopathic plasmacytic lymphadenopathy (IPL), which is characterized by hypergammaglobulinemia, i.e., high levels of serum immunoglobulins, and histologically mature plasma cell proliferation in the lymph nodes, is considered a part of iMCD-NOS due to their clinicopathological similarity. However, till date, no study has validated if IPL has distinct clinicopathologic features compared to other iMCD-NOS. This motivated a team of researchers led by Assistant Professor Asami Nishikori, including Associate Professor Midori Filiz Nishimura, and Professor Yasuharu Sato from Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences, Japan to conduct a thorough clinicopathological examination of IPL and others in iMCD. Their findings were published on September 7, 2022, in the International Journal of Molecular Sciences. "We wanted to determine whether IPL has distinct and uniform clinicopathologic features compared to other subtypes (non-IPL) in iMCD-NOS," remarks Assist. Prof. Nishikori while discussing the motivation behind the study. The team analyzed lymph node specimens derived from 42 Japanese patients with lymph node involvement of iMCD-NOS, who met the consensus diagnostic criteria of iMCD and were negative for KSHV/HHV8 infections. Upon further examination, the team classified 34 of the 42 patients as the IPL group and the remaining 8 as the non-IPL group. On grading histological features such as vascularity, plasmacytosis (high proportion of plasma cells), atrophic and hyperplastic germinal centers (GCs), the team identified significant pathological differences between the specimens of the IPL and non-IPL groups. The IPL group demonstrated greater plasmacytosis and hyperplastic GCs compared to the non-IPL group. Conversely, the vascularity of the non-IPL group was higher than that of the IPL group. Clinically, the IPL group exhibited higher platelet count and serum antibody (immunoglobulin G) levels, with lesser fluid retention in pleural and/or abdominal cavity. The frequency of disease-specific autoantibody detection was also different between the groups. In addition, the clinical course and treatment responses in the two groups were also distinct. Upon treatment with tocilizumab, an anti-interleukin 6 receptor monoclonal antibody approved to treat iMCD in Japan, there was a significant improvement in the condition of patients with IPL. In contrast, patients with non-IPL responded poorly to the drug and showed progressed disease activity, requiring more intensive treatment. These findings were consistent with those of previous studies that suggest that the clinical course of IPL disease progression is slower as compared to the non-IPL group, and with a superior response to anti-IL-6 agents. Discussing these findings, Assist. Prof. Nishikori states "Given the heterogeneity of non-IPL cases, we must try to identify its primary cause. Molecular analysis could lead to a better understanding of disease pathology and the development of subsequent targeted therapies." To sum up, these findings have established IPL as a clinicopathologically uniform disease, which can be reclassified into an independent subtype of iMCD. So, what are the future implications of these findings? "It is critical that patients get the most out of any treatment modules. Studies on iMCD subtype-specific diagnostic biomarkers, treatment, and follow-up are thus warranted in the future to improve the clinical outcomes for these patients," concludes Assist. Prof. Nishikori.

Chewed plants are helping veterinarians provide personalized health care to wild, endangered mountain gorillas in East Africa. A mountain gorilla walks in the forest of East Africa's Virunga Volcanoes conservation area. It stops at a piece of wild celery, sits down, and begins to chew. It strips the vegetable's fibrous threads through its teeth, extracting the fleshy, juicy bits, then drops the chewed stalk on the ground and ambles away. Minutes later, wildlife veterinarians observing the scene write down the name of the gorilla and retrieve the saliva-drenched plant, which carries vital information about that gorilla's health. This simple, noninvasive tool of a chewed plant is helping Gorilla Doctors -- who know each gorilla by name -- provide personalized health care to wild, endangered mountain gorillas living in Rwanda, Democratic Republic of Congo (DRC) and Uganda. Scientists from the University of California, Davis, used the technique to rule out the presence of human herpesviruses among the region's mountain gorillas. Their findings are described in a study published in the American Journal of Primatology. Gorilla Doctors is a partnership between the Karen C. Drayer Wildlife Health Center or WHC, within the UC Davis School of Veterinary Medicine and the Mountain Gorilla Veterinary Project. The program monitors the health of mountain gorillas and provides veterinary care to injured and ill gorillas. Individual care While a human herpesvirus may amount to no more than a cold sore in a person, it could be more serious if introduced to gorillas or other species. After extracting the DNA from the discarded plants and screening them for orally shed pathogens, the study found no evidence of human herpesviruses infection among the free-ranging gorillas. "We were able to do this study entirely using chewed plants," said lead author Tierra Smiley Evans, research faculty with the WHC and One Health Institute at UC Davis. "That allowed us to collect specimens from every known, habituated mountain gorilla in Uganda and Rwanda. This shows we can monitor gorillas -- and potentially other primate species -- over time, noninvasively, at the individual level and help answer questions regarding their conservation." Staying vigilant Gorilla trekking in this region is a major draw, and the wild gorillas here are accustomed to humans. While gorilla tourism incentivizes the conservation of their habitat, it also requires a high level of care to prevent people and gorillas from exchanging diseases. The study's finding that human herpesviruses have not spilled over indicates that guidelines Gorilla Doctors and gorilla management authorities use to limit the distance between humans and gorillas in the park are helping to prevent the spread of disease. It also serves as a reminder to stay vigilant to prevent novel viruses from entering the population. "Gorilla Doctors research has proven that human viruses cause respiratory disease in endangered mountain gorillas," said co-author Kirsten Gilardi, DVM, executive director of the Gorilla Doctors and director of the WHC at UC Davis. "Dr. Evans' research findings that human herpesviruses were not detected in gorilla saliva was reassuring. It's further evidence that park rules for gorilla visitation, like wearing face masks and keeping a minimum distance of 23-33 feet, are effective in reducing the risk of transmission of human diseases to mountain gorillas." Gorilla IDs Chewed plant analysis is a relatively new tool for Gorilla Doctors to provide personalized care to this endangered species. Face time, of course, is also important, and the Gorilla Doctors and rangers know individual gorillas by sight. Such recognition is greatly aided by the wrinkles above each gorilla's nose. Mountain gorillas have distinct noseprints used by veterinarians and rangers to identify them, much how fingerprints are used to identify people. Evans said the personalities and dramas of gorilla life become quickly apparent when observing mountain gorillas. Evans recalls watching a young male gorilla a decade ago when she was collecting samples for her Ph.D. studies. "He was in his teen years and always causing problems. He was also my favorite because he was an interesting, very inquisitive guy," she said. "I recently went back, and there, 10 years later, is this chill, big silverback, with babies crawling all over him. Someone said, 'That's Kabukojo.' I said, 'You're kidding me!' We'd all gotten older; we'd all changed." The study's additional co-authors include Linda Lowenstine, Benard Ssebide, Peter Barry, Fred Nizeyimana, Jean Bosco Noheli, Ricky Okello, Michael Cranfield, Jonna Mazet and Christine Kreuder Johnson of UC Davis; Jean Felix Kinani of the One Health Approach for Conservation in Rwanda; and Antoine Mudakikwa of the Rwanda Development Board. The research was funded by the William J. Fulbright Program, U.S. Agency for International Development and the National Institutes of Health.