Introduction: Pathogenetic relationship of aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) was registered a long time ago. Approximately in 50-60% of patients with AA is detected PNH-clone, and during long-term observation the transformation of AA into classic PNH is likely. At the time of diagnosis PNH-clone sizes range from small proportion of PNH-cells, requiring only monitoring, up to combination of clinically manifested AA and PNH requring combined therapy. Nevertheless, the peculiar characteristics of the disease in cases of different AA-PNH-combinations still remain unclear. Aim: to evaluate the relationship between size and dynamics of PNH-clone with clinical features of AA/PNH. Materials and methods: We have evaluated blood samples of 81 patients with AA (whole group) for the presence of PNH-clone using flow cytometry according to ICCS standards. 23 patients aged 23 to 54 years (median 46 years) were under constant observation for 3 years or more, control examination was performed once every 6 months (dynamic observation group). Of them 17 had severe AA (SAA) and 6 - nonsevere AA (NAA). Twelve patients received standard immunosupressive therapy (IST) for the treatment of AA, other patients were in remission and did not require IST. Results: In the whole group of patients (n=81) 47 patients (58%) were AA/PNH-positive (PNHpos) with clone size ranging from 0.01% to 97.9%. PNH-clone less than 1% was identified in 10% of subjects; PNH-clone more than 10% was observed in 50% of subjects. In dynamic observation group 18 patients were AA/PNHpos with initial clone size from 0.1% to 95.9%, and 5 patients - AA/PNH negative (AA/PNHneg). In AA/PNHneg patients pathological clone still has not been detected in repeated studies for the observed period. Among patients with AA/PNHpos stable clone was observed in 11 subjects (61%), it increased to 10% and more in 5 subjects (28%) and decreased in 2 patients (11%) with small PNH-clone. Clinical and laboratory signs of chronic intravascular hemolysis were usually observed in patients with pathological clone over 25%. PNH-clone less than 10% was not accompanied by significant deviations in clinico-laboratory indices. Most of patients in whom PNH-clone size increased, had remission of AA. Four patients had clonal evolution to manifest classical PNH, of them in 2 patients with SAA аplasia of hematopoiesis persisted. In one patient, with complete remission of SAA lasting more than 3 years and minor PNH-clone, was observed transformation into myeloid leukemia leading to death. Ekulizumab was prescribed to 4 patients: 2 with clinically manifest hemolysis and clone size > 90% (1 - in conjunction with IST for AA), and 2 with clone size 24% and 70% and LDH > 1.5 ULN due to unplanned pregnancies (both on Cyclosporin therapy). All of them achieved the target level of LDH <1.5 ULN in the first 2 weeks of therapy. Of 2 transfusion-dependent patients, one still does not require transfusion support after the Ekulizumab initiation, and in other patient transfusion dependency decreased, despite refractory TAA. In one patient with PNH-clone 70% Ekulizumab therapy was initiated in III trimester of pregnancy, delivery was without complications, full-term baby, 8-9 points Apgar. In the 2nd pregnant patient with PNH-clone 24% Ekulizumab was prescribed because of pre-eclampsia and LDH>4 ULN at 21-22 weeks with antenatal fetal death, and it allowed for accelerating cure of pathological symptoms. Conclusion: PNH-clone was detected in 58% of patients with AA. Our data confirm the need for monitoring of PNH clone in patients with AA and for timely adequate therapy, including inhibitors of intravascular hemolysis, according to specific indications in each case. Disclosures Fominykh: Novartis Pharma: Honoraria; BMS: Honoraria.
Recent studies devoted to the patterns of the COVID-19 course in patients of various groups indicate a significant role of the immunity state in the disease development. Risk groups of severe disease course, including senile age, obesity and immunodeficiency conditions, have been identified. Research is underway to identify the genetic predisposition to SARS-CoV-2 infection and determine the poor prognosis in COVID-19. The presented article examines the immunological aspects of pathological conditions associated with an unfavorable prognosis of COVID-19. A complex immune response (including both innate immune mechanisms and an adaptive systemic response) develops in response to SARS-CoV-2 infection. The key mechanism of multisystem organ failure is a hyperimmune reaction with the development of a systemic inflammatory response, the so-called "cytokine storm", and the characteristics of the immune response largely determine the disease severity. In this regard, the immune response characteristics in patients at risk are of particular interest, including studies concerning the immunological aspects of a more severe disease course depending on age, the history of obesity, diabetes mellitus and other pathological conditions, as well as various genetic factors, which is the subject of active study at present. KEYWORDS: immune system, COVID-19, SARS-CoV-2, risk factors, obesity, oncological diseases, genetic predisposition, immune response. FOR CITATION: Glazanova T.V., Shilova E.R., Pavlova I.E. Risk factors of COVID-19: immunological aspects. Russian Medical Inquiry. 2023;7(11). (in Russ.). DOI: 10.32364/2587-6821-2023-7-11-5.
Актуальность и цели. Пароксизмальная ночная гемоглобинурия (ПНГ)-заболевание, обусловленное приобретенным клональным нарушением гемопоэтических стволовых клеток с повышенной чувствительностью мембраны клеток клона к комплементу. ПНГ может быть как самостоятельным заболеванием, так и связанным с другими патологическими состояниями, характеризующимися костномозговой недостаточностью, в первую очередь с апластической анемией (АА). При АА, ассоциированной с ПНГ (АА/ПНГ), величина патологического клона исходно может быть различной. У части больных наблюдается постепенное нарастание ПНГ-клона, появление признаков внутрисосудистого гемолиза и трансформация в классическую гемолитическую ПНГ. В таком случае важно оценить клиническую ситуацию и определить наличие показаний к терапии ингибиторами комплемента. В ходе таргетной терапии необходимо оценить эффективность лечения, основанного на контроле комплемент-обусловленного гемолиза, и определить возможные причины недостаточного эффекта. Материалы и методы. Работа построена на обсуждении 1 клинического наблюдения. Пациентка, 1964 г.р., с первичным диагнозом АА находилась под наблюдением в ФГБУ «Российский НИИ гематологии и трансфузиологии ФМБА» с 1989 г. по настоящее время. Лечение больной включало гемокомпонентную терапию, антилимфоци
Introduction Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematopoietic stem cell disease that can lead to life-threatening complications including thrombotic events (TE), chronic kidney disease (CKD) and pulmonary hypertension. An international PNH Registry was implemented in 2008 to enhance understanding of the natural history of PNH, to describe treatment outcomes, and to evaluate the long term safety of eculizumab in treated patients. Methods This Registry is a non-interventional, prospective, multicenter, observational study. All patients with a diagnosis of PNH (confirmed in accordance with international diagnostic guidelines) or a detected PNH clone are enrolled irrespective of age or therapy. Data on patient demographics, medical histories, disease characteristics and treatment are collected at enrollment, every 6 months thereafter and/or at discontinuation. Descriptive statistics are used to describe the data; n, median and range (min–max) for continuous variables and percentages for categorical parameters. Results As of May 1, 2013, the Registry has enrolled 248 patients from Russia, over 50% of whom have a history of aplastic anemia or other bone marrow disorder (BMD) (Table 1). Disease characteristics for the overall population and by clone size or LDH level are presented in table1.A total of 25 patients have received eculizumab and have available follow-up data after starting treatment; median (range) follow-up time 4.4 (0.3–8.3) months. Among the 11 patients treated with eculizumab and with available LDH levels, the median LDH ratio was 5.7 X ULN before treatment and 1.0 X ULN at last follow-up assessment. Conclusion Russian patients included in the International PNH Registry show broad ranges of age, clone size, and degrees of hemolysis. History of TE, impaired renal function, and signs of chronic hemolysis are present among these patients regardless of PNH clone size. History of TE was recorded more frequently in patients with PNH clone sizes ≥20%, and was also more frequent among patients with LDH levels ≥1.5 x ULN. Among patients treated with eculizumab there was a marked decrease in hemolysis (as measured by LDH levels). Disclosures: Lisukov: Alexion: Honoraria. Kulagin:Alexion: Honoraria. Shilova:Alexion: Honoraria. Afanasyev:Alexion: Honoraria.
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