ABSTRACT
Background: COVID-19 may be more severe in persons with HIV (PWH). However, underlying biological mechanisms associated with the development of COVID-19 and its clinical severity among antiretroviral therapy (ART) treated PWH are largely unknown. Therefore, we wished to evaluate temporal changes in plasma proteins following SARS-CoV-2 infection and identify pre-infection proteomic markers associated with future COVID-19. Method(s): We analyzed the data of clinical, antibody-confirmed COVID-19 ARTtreated PWH from the global Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE). Individuals were matched on geographic region, age, and sample timing to antibody-negative controls. For cases and controls, pre-COVID-19 pandemic specimens were obtained prior to January 2020 to assess temporal changes and baseline differences in protein expression in relationship to COVID-19 severity, using mixed effects models adjusted for false-discovery rate. Result(s): We compared 257 unique plasma proteins (Olink Proteomics) in 94 COVID-19 antibody-confirmed clinical cases and 113 matched antibody-negative controls, excluding COVID-19 vaccinated participants (median age 50 years, 73% male). 40% of cases were characterized as mild;60% moderate to severe. Median time from COVID-19 infection to follow-up sampling was 4 months. Temporal changes in protein expression differed based on COVID-19 disease severity. Among moderate to severe cases vs. controls, NOS3 increased, whereas ANG, CASP-8, CD5, GZMH, GZMB, ITGB2, and KLRD1 decreased. Higher baseline circulating concentrations of granzymes A, B and H (GZMA, GZMB and GZMH) were associated with the future development of moderate-severe COVID-19 in PWH and were related to immune function, including CD4, CD8 and the CD4/ CD8 ratio. Conclusion(s): We identified temporal changes in novel proteins in closely linked inflammatory, immune, and fibrotic pathways which may relate to COVID-19-related morbidity among ART-treated PWH. Further, we identified key granzyme proteins, serine proteases expressed by cytotoxic T lymphocytes and NK cells in response to foreign antigens, associated with future COVID-19 in PWH. Our results provide unique insights into the biological susceptibility and responses to COVID-19 infection in PWH. (Figure Presented).
ABSTRACT
The studies on humoral immune response in the individuals who have undergone COVID-19 and vaccinated with anti-COVID vaccines allows us to assess the development of "hybrid" immunity, which contributes to understanding the mechanisms of its formation from the effector phase to the step of immunological memory. We assessed the relative and absolute contents of B cell populations and subpopulations, development of humoral immunity in the patients who suffered with COVID-19 of varying severity being thereafter vaccinated with "KoviVak" and "Sputnik V". The study involved volunteers (age 47.3+/-14.5 years) who beared COVID-19 asymptomatically (n = 32), at moderate severity (n = 21), or had severe form of the disease (n = 12), then being vaccinated with "KoviVak" and "Sputnik V" 6-9 months after their recovery. The groups of vaccinated persons consisted of those who beared severe disease being vaccinated with "KoviVak" (n = 6) or "Sputnik V" (n = 6);moderate cases, vaccinated with "KoviVak" (n = 10) and "Sputnik V" (n = 11);asymptomatic cases vaccinated with "KoviVak" (n = 10) and "Sputnik V" (n = 22). We have determined relative and absolute numbers of B lymphocytes (CD45+CD19+), B1 lymphocytes (CD45+CD5+CD19-CD27-), B2 lymphocytes (CD45+CD19+CD5-CD27-), total population of memory B cells (CD45+CD19+CD5-CD27+), non-switched (CD45+CD19+IgD+CD27+), and switched (CD45+CD19+IgD-CD27+) memory B cells;mature naive B lymphocytes (CD45+CD19+CD27-IgD+), plasmoblasts (CD45+CD19+ CD38+++IgD-CD27+), as well as presence of IgG to S(RBD)-SARS-CoV-2 protein. We have found that the humoral immunity among survivors of COVID-19 of varying severity is expressed for up to nine months. The largest number of volunteers who raised antibodies to SARS-CoV-2 S-protein was registered in the group of seriously ill patients. As soon as 1 month after "Sputnik V" vaccination and until the end of the observation, all the examined subjects in this group became seropositive. 4-5 months after injection of this vaccine, specific immunoglobulins were present in all patients who had asymptomatic or average-severity infection. All volunteers who received "KoviVak" had antibodies to the COVID-19 viral S protein from the beginning to the end of the study. Vaccination, especially with "KoviVak", contributed to the highest increase, both in relative and absolute numbers of memory B lymphocytes in asymptomatic patients. Less pronounced changes in the content of B lymphocytes in COVID-19 patients who had severe and moderate clinical course may be associated with higher levels of these cells prior to injection of the vaccines. A positive correlation was found between the number of memory B cells and presence of immunoglobulins to the S protein SARS-CoV-2 in all examined patients.Copyright © 2023 Russian Association of Allergologists and Clinical Immunologists, St. Petersburg Regional Branch (SPb RAACI). All rights reserved.
ABSTRACT
The studies on humoral immune response in the individuals who have undergone COVID-19 and vaccinated with anti-COVID vaccines allows us to assess the development of "hybrid" immunity, which contributes to understanding the mechanisms of its formation from the effector phase to the step of immunological memory. We assessed the relative and absolute contents of B cell populations and subpopulations, development of humoral immunity in the patients who suffered with COVID-19 of varying severity being thereafter vaccinated with "KoviVak" and "Sputnik V". The study involved volunteers (age 47.3+/-14.5 years) who beared COVID-19 asymptomatically (n = 32), at moderate severity (n = 21), or had severe form of the disease (n = 12), then being vaccinated with "KoviVak" and "Sputnik V" 6-9 months after their recovery. The groups of vaccinated persons consisted of those who beared severe disease being vaccinated with "KoviVak" (n = 6) or "Sputnik V" (n = 6);moderate cases, vaccinated with "KoviVak" (n = 10) and "Sputnik V" (n = 11);asymptomatic cases vaccinated with "KoviVak" (n = 10) and "Sputnik V" (n = 22). We have determined relative and absolute numbers of B lymphocytes (CD45+CD19+), B1 lymphocytes (CD45+CD5+CD19-CD27-), B2 lymphocytes (CD45+CD19+CD5-CD27-), total population of memory B cells (CD45+CD19+CD5-CD27+), non-switched (CD45+CD19+IgD+CD27+), and switched (CD45+CD19+IgD-CD27+) memory B cells;mature naive B lymphocytes (CD45+CD19+CD27-IgD+), plasmoblasts (CD45+CD19+ CD38+++IgD-CD27+), as well as presence of IgG to S(RBD)-SARS-CoV-2 protein. We have found that the humoral immunity among survivors of COVID-19 of varying severity is expressed for up to nine months. The largest number of volunteers who raised antibodies to SARS-CoV-2 S-protein was registered in the group of seriously ill patients. As soon as 1 month after "Sputnik V" vaccination and until the end of the observation, all the examined subjects in this group became seropositive. 4-5 months after injection of this vaccine, specific immunoglobulins were present in all patients who had asymptomatic or average-severity infection. All volunteers who received "KoviVak" had antibodies to the COVID-19 viral S protein from the beginning to the end of the study. Vaccination, especially with "KoviVak", contributed to the highest increase, both in relative and absolute numbers of memory B lymphocytes in asymptomatic patients. Less pronounced changes in the content of B lymphocytes in COVID-19 patients who had severe and moderate clinical course may be associated with higher levels of these cells prior to injection of the vaccines. A positive correlation was found between the number of memory B cells and presence of immunoglobulins to the S protein SARS-CoV-2 in all examined patients.Copyright © 2023 Russian Association of Allergologists and Clinical Immunologists, St. Petersburg Regional Branch (SPb RAACI). All rights reserved.
ABSTRACT
In the context of the COVID-19 pandemic, scientific interest is growing in studying the impact of the proposed vaccination on women's reproductive health. As is known, alterations in the state of the immune system and activation of an autoimmune response can lead to reproductive failure in women and potential complications of subsequent pregnancy. Objective(s): to evaluate the effect of the "Gam-COVID-Vac" on the immune status parameters, the relationship of their changes and the specific immune response to vaccination with the dynamics of the level of autoantibodies in women of reproductive age. The prospective study included 120 women who were vaccinated against COVID-19 with the "Gam-COVID-Vac". The criteria for inclusion in the study were: the age from 18 to 49 years, the absence of COVID-19 in the anamnesis, a negative result of a study on SARS-CoV-2 by PCR and negative results of tests for antibodies of classes G and M to SARS-CoV-2 before vaccination, the absence of pregnancy and serious somatic diseases. The patients were examined twice: immediately before vaccination and 90-100 days after the introduction of the 1st component of the vaccine. The level of IgG antibodies to SARS-CoV-2 after vaccination was assessed using ELISA. Before and after vaccination, the levels of antiphospholipid, anti-nuclear, organ-specific and antihormonal autoantibodies were determined, peripheral blood lymphocytes were immunophenotyped to determine the main subpopulations (CD3, CD4, CD8, CD19, CD5, CD16, CD56), as well as the expression of activation markers of lymphocytes (HLA-DR, CD25, CD147) using monoclonal antibodies. The effectiveness and safety of the combined vector vaccine against COVID-19 were high. Specific IgG antibodies to SARS-CoV-2 were produced in 98.3% of vaccinated women, no serious adverse reactions were observed. After vaccination, there was an increase in the level of some autoantibodies within the reference ranges, only IgM antibodies to phosphatidylethanolamine (PE) and IgG antibodies to DNA increased above the reference values. However, this increase was transient. After vaccination, the following changes in the parameters of the immunogram were observed: an increase in the content of cells with CD3+CD25+, CD19+ phenotype in peripheral blood and a decrease in the content of cells with CD56+CD16+ phenotype within the reference ranges, a decrease in CD147+/CD3+. Weak correlations were noted between these changes in immunogram parameters and the levels of some autoantibodies. The specific antiviral immune response to vaccination did not correlate with the autoimmune response. Vaccination with "Gam-COVID-Vac" is effective and safe and does not lead to disorders in the immune system. The observed increase in the level of autoantibodies to PE and DNA is transient. Changes in the parameters of the immune status within the reference ranges may be due to vaccination and the development of a specific antiviral immune response. Copyright © 2022, SPb RAACI.
ABSTRACT
In the context of the COVID-19 pandemic, scientific interest is growing in studying the impact of the proposed vaccination on women's reproductive health. As is known, alterations in the state of the immune system and activation of an autoimmune response can lead to reproductive failure in women and potential complications of subsequent pregnancy. Objective: to evaluate the effect of the "Gam-COVID-Vac” on the immune status parameters, the relationship of their changes and the specific immune response to vaccination with the dynamics of the level of autoantibodies in women of reproductive age. The prospective study included 120 women who were vaccinated against COVID-19 with the "Gam-COVID-Vac”. The criteria for inclusion in the study were: the age from 18 to 49 years, the absence of COVID-19 in the anamnesis, a negative result of a study on SARS-CoV-2 by PCR and negative results of tests for antibodies of classes G and M to SARS-CoV-2 before vaccination, the absence of pregnancy and serious somatic diseases. The patients were examined twice: immediately before vaccination and 90-100 days after the introduction of the 1st component of the vaccine. The level of IgG antibodies to SARS-CoV-2 after vaccination was assessed using ELISA. Before and after vaccination, the levels of antiphospholipid, anti-nuclear, organ-specific and antihormonal autoantibodies were determined, peripheral blood lymphocytes were immunophenotyped to determine the main subpopulations (CD3, CD4, CD8, CD19, CD5, CD16, CD56), as well as the expression of activation markers of lymphocytes (HLA-DR, CD25, CD147) using monoclonal antibodies. The effectiveness and safety of the combined vector vaccine against COVID-19 were high. Specific IgG antibodies to SARS-CoV-2 were produced in 98.3% of vaccinated women, no serious adverse reactions were observed. After vaccination, there was an increase in the level of some autoantibodies within the reference ranges, only IgM antibodies to phosphatidylethanolamine (PE) and IgG antibodies to DNA increased above the reference values. However, this increase was transient. After vaccination, the following changes in the parameters of the immunogram were observed: an increase in the content of cells with CD3+CD25+, CD19+ phenotype in peripheral blood and a decrease in the content of cells with CD56+CD16+ phenotype within the reference ranges, a decrease in CD147+/CD3+. Weak correlations were noted between these changes in immunogram parameters and the levels of some autoantibodies. The specific antiviral immune response to vaccination did not correlate with the autoimmune response. Vaccination with "Gam-COVID-Vac” is effective and safe and does not lead to disorders in the immune system. The observed increase in the level of autoantibodies to PE and DNA is transient. Changes in the parameters of the immune status within the reference ranges may be due to vaccination and the development of a specific antiviral immune response. © 2022, SPb RAACI.
ABSTRACT
Introducao: O acometimento do sistema nervoso central (SNC) e raro nas doencas linfoproliferativas B cronicas, sendo mais frequente a recaida nos linfomas nao-Hodgkin agressivos, porem a era pos Rituximab promoveu um ganho para esse perfil de pacientes. Objetivo: Relatar o envolvimento de SNC em 04 pacientes com doencas linfoproliferativas B cronicas e indolentes e revisar a literatura. Relato de caso: Caso 1: Homem, 53 anos, com leucemia linfoide cronica (LLC) Binet A desde 2012 e delecao 17p, apresentou crise convulsiva e rebaixamento neurologico em 12/2021. O liquor mostrou 18,3% de celulas B CD5+, CD19+, CD200+, recebeu imunoquimio intratecal e ibrutinibe sem resposta, LCR ainda infiltrado. Caso 2: Homem, 56 anos, com LLC Binet A desde 07/2021 evoluiu com abrupta piora cognitiva, RNM encefalica previa normal, novo exame em 02/2022 mostrou lesoes expansivas infiltrativas e nodulares intra-axiais bilaterais, compativeis com LNHDGCB (BCL-2+, CD20+, c-Myc+, Ki-67+, MUM1+), LCR normal, tratado com metotrexate (MTX) em altas doses, sem resposta. Caso 3: Mulher, 56 anos, com LNH folicular EC IVA em 2019, recebeu 06 ciclos de R-CHOP e manutencao por 02 anos, em remissao clinica. Em 04/2022 cursou com rapido agravo neurologico. A RNM mostrou lesoes na substancia branca nos hemisferios cerebrais, LCR infiltrado por celulas CD19, CD23, CD20, CD10 positivas, tratada com Ara C em altas doses, regressao das lesoes encefalicas, LCR ainda infiltrado. Caso 4 - Homem, 64 anos, com linfocitose, assintomatico desde 2011, IF de SP CD5- CD20+, CD22+, CD79b+, CD200+, evoluiu em 01/2022 subitamente com rebaixamento neurologico, entubado, LCR com 52,8% de linfocitos B CD19+, CD 20+, CD200+. Intercorreu com infeccao pelo SARS-Cov 19, complicacoes clinicas e obito. Discussao: O envolvimento do SNC nas doencas linfoproliferativas, tanto na apresentacao inicial ou na recidiva, e raro, podendo ser leptomeningeo disseminado e/ou parenquimatoso. Raramente descrito, o acometimento meningeo na LLC e objeto de discussao quanto ao impacto prognostico e ao tratamento. A infiltracao do SNC e mais descrita nos linfomas agressivos em cerca de 5% dos casos. Descrevemos 04 casos com envolvimento SNC em patologias de comportamento tipicamente indolente. Lemma et al. exploraram o papel dos marcadores biologicos que podem conferir as celulas do linfoma tropismo pelo SNC, altos niveis de Integrina alpha 10 e PTEN em amostras de tecido foram associadas a este tropismo, enquanto a expressao de CD44 e caderina-11 parecem ser protetivas, estes dados sao preliminares e precisam de validacao. A apresentacao clinica e heterogenea, desde alteracao comportamental, cefaleia, meningismo, hidrocefalia, e hipertensao intracraniana. No tratamento do linfoma primario de SNC o MTX e fundamental, mas ainda nao ha consenso em relacao a profilaxia e ao protocolo padrao nas recaidas. Fica claro que a dose de MTX IT parece insuficiente para tratar as formas parenquimatosas. Quando ha envolvimento meningeo, a via IT pode ser usada, mas os dados sobre os resultados nao sao conclusivos. Conclusao: O tratamento dos pacientes que apresentam infiltracao SNC permanece um desafio principalmente nos linfomas indolentes, considerando a dificuldade de padronizar tratamento eficaz, de menor toxicidade e a gravidade das sequelas por vezes irreversiveis. O mecanismo associado a invasao e a predilecao de alguns casos pelo SNC permanece incerto. Copyright © 2022
ABSTRACT
Objetivo: Descrever dois casos com desfechos diferentes de linfoma hepatoesplenico de celulas T gamma-delta (LHECTGD), entidade rara que corresponde a menos de 1% dos linfomas nao-Hodgkin. Caso clinico: Caso 1: Feminina, 71 anos, portadora de artrite reumatoide, HAS e glaucoma, internada por pancitopenia e pneumonia bacteriana sobreposta a infeccao por COVID-19. Fazia seguimento ha 2 anos com hematologia por anemia e plaquetopenia, sem exames diagnosticos. Em avaliacao medular, imunofenotipagem de medula compativel com linfoma T hepatoesplenico (LTHE). Devido intercorrencias infecciosas, paciente evoluiu para obito antes do tratamento da doenca hematologica. Caso 2: Masculino, 47 anos, avaliado em servico de hematologia devido hepatoesplenomegalia, baco ate 15cm do rebordo costal esquerdo (RCE), pancitopenia com neutropenia grau IV em hemograma inicial, descartadas infeccoes virais e leishmaniose visceral. Em avaliacao medular, biopsia de medula ossea evidenciou infiltracao por doenca linfoproliferativa B e imunohistoquimica inconclusiva. Imunofenotipagem de aspirado de medula ossea compativel com infiltracao por LTHE. O paciente recebeu tratamento com 6 ciclos de CHOEP e encontra-se com normalizacao de hemograma apos ultimo nadir, resposta clinica (reducao do baco para 3cm RCE e melhora dos sintomas B), alem de resposta em imagem no exame PET-CT. Atualmente, transplante autologo em andamento no intuito de consolidacao de resposta. Discussao: O LHECTGD tem pico de incidencia em adolescentes e adultos jovens e uma razao homem/mulher de 9:1. E uma doenca rara, visto que a maioria dos linfomas de celulas T expressa receptores alfa-beta e apenas 2-4% expressam receptores gamma-delta. Atualmente ha pouco mais de cem casos descritos na literatura, sendo definido como um linfoma de proliferacao maligna de celulas T nos sinusoides do figado, na polpa vermelha do baco e na medula ossea. O fenotipo frequentemente exposto e de celulas T CD2+, CD3+, CD4-, CD5-, CD7+-, CD8-, com expressao de receptor celula T gama delta ou alfa beta. Dentre as anormalidades citogeneticas associadas, inclui-se o isocromossomo 7q com ou sem trissomia do 8. Clinicamente, os pacientes apresentam sintomas B, alem de hepatoesplenomegalia acentuada, sem adenomegalias suspeita, o que aumenta o desafio diagnostico e leva a inferencias diagnosticas infecciosas e de hipertensao portal antes do diagnostico hematologico. O tratamento engloba desde a intervencao cirurgica, como a esplenectomia - no intuito de controlar o hiperesplenismo e evitar uma das principais causas de obito, a ruptura esplenica -, alem de quimioterapias baseadas em regimes que contenham etoposideo, sem esquemas com relato de superioridade na literatura. O transplante autologo (e em alguns relatos, o alogenico) foram indicados para consolidacao quando ha resposta ao tratamento. Conclusao: O LHETGD e uma doenca rara, de prognostico reservado, com multiplos relatos de atraso diagnostico devido a ausencia de sintomas especificos da doenca. Recomenda-se, assim, que, diante de paciente jovens, com quadro de trombocitopenia ou alteracoes de outras linhagens e hepatoesplenomegalia, a hipotese diagnostica de LHECTGD deve ser considerada. Em relacao ao arsenal terapeutico disponivel atualmente, novos estudos mostram-se necessarios, objetivando melhorar a expectativa e qualidade de vida dos pacientes. Copyright © 2022
ABSTRACT
Chronic lymphocytic leukaemia is a haematological malignancy that occurs due to an increased proliferation of mature B lymphocytes. It is considered to be the most common leukaemia in adults. Hyponatremia is commonly seen in such patients. This case report is about a 75-year-old male, who presented with giddiness, followed by altered sensorium. However, the patient had no motor weakness or sensory loss. Initially, a diagnosis of posterior circulation stroke was made but Magnetic Resonance Imaging (MRI) brain did not show associated signs. The routine investigations showed highly elevated total leukocyte count and hyponatremia. The patient was worked up for malignancy and diagnosed with Chronic lymphocytic leukaemia. Oncology reference was taken and treated with tablet Ibrutinib. On discharge, the patient's mentation improved, and he is on regular follow-up.
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Objectives: A 36-year-old Caucasian woman developed acute hepatitis and morbilliform eruption arising ten days after the first dose of the mRNA BNT162b2 SARS-CoV-2 vaccine. Materials and Methods: The patient was asymptomatic apart from the skin rash. Liver function tests showed predmoninantly severe transaminitis (AST 523 U/L, ALT 1550 U/L, GGT 151 U/L, ALP 128 U/L, bilirubin 12 umol/L). Only the ANA 1:160 was abnormal. Other serology for autoimmune and infectious diseases were negative. Multiphase computed tomography of the abdomen was unremarkable. The SARS-CoV-2 anti-spike IgG titre was 67.5 AU/mL (cut-off[15 AU/mL). The skin histology revealed spongiotic reaction pattern with focal interface lymphocytic inflammation. Multiple eosinophils and a few plasma cells were present. The epidermal lymphocytes were composed of CD2, CD3, C4, CD5, CD7 and CD8-positive T cells, with a CD4:CD8 ratio of 1:5. A small number stained positive with TIA1, PD1 and granzyme B. CD56 staining was negative. A liver biopsy was performed after 2 days of steroids. Liver histology showed mild steatosis and mild inflammatory portal infiltrate comprising mainly of small lymphocytes that were CD3 positive with retained staining for CD7 and CD8. Lobular architecture was preserved with inconspicuous interface hepatitis or piecemeal necrosis. Results: The patient was treated with intravenous hydrocortisone (400 mg/day) followed by prednisone (50 mg/day). There was rapid improvement in her liver function tests and cutaneous manifestations (Fig. 1). Conclusion: mRNA COVID-19 vaccine induced hepatitis is a rare phenomenon that is steroid-responsive and has associations with cutaneous eruptions. Our patient's lack of hepatic histological abnormalties is most likely due to early immunosuppression. She had epidermal lymphocytosis with predominance of CD8-positive T cells that were not of cytotoxic phenotype and we are uncertain as to their significance. There is limited guidance on the safety of SARS-CoV-2 vaccination in those who have had developed significant hepatic and cutaenous reactions. Further work is needed.
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Introduction: In January 2020, the genome of the novel coronavirus, SARS-CoV-2, was sequenced, the etiologic RNA virus for COVID- 19. Several variants from the initial strain of SARS-CoV-2 have been reported, notably the Delta variant and most recently, the Omicron variant. However, how the virus affects the cellular immune system has been elusive. This study aims to investigate peripheral blood immunophenotype, natural killer (NK) cell cytotoxicity, and T helper (Th) 1/ Th2 ratios in pregnantwomen undergoing immunotherapy with a history of recurrent pregnancy losses (RPL) and repeated implantation failures (RIF). Materials and Methods: A prospective cohort study was performed on pregnant women with a history of RIF and RPL. The study group comprised 20 pregnant women with COVID-19, of whom eight had documented vaccinations. All were undergoing personalized immunemodulation and/or anticoagulation treatment. When they were diagnosed with COVID-19, immunomodulating medications were tapered off or decreased until recovery. Peripheral blood immunophenotype, NK cell cytotoxicity (NKC) at effector to target cell (E: T) ratio at 50:1 and 25:1, and Th1/Th2 cell ratios (TNF-a/IL-10, IFN-g/IL-10 producing Th cell ratios)were measured by flow cytometry within 5weeks before and after COVID-19. Statistical analysis was performed by using the student t-test. Results: Peripheral blood immunophenotypes including % CD3 (77.38 ± 2.15 % vs. 79.98 ± 1.65 %, P = 0.34), % CD19 (13.63 ± 1.63 % vs. 12.63 ± 1.79 %, P = 0.68), % CD56 (7.61 ±1.32 % vs. 6.15± 1.08 %, P = 0.40), % CD19/CD5 (4.68 ±1.41 % vs. 4.17 ± 0.72 %, P = 0.75) were not significantly different before and after COVID- 19. NKC at E: T ratio of 50:1 (Mean ±SE), before and after COVID- 19 were 21.16 ± 0.66% and 22.21 ± 1.06 % respectively (P = 0.40). NKC at E: T cell ratios of 25:1 were 15.71 ± 0.69 % and 16.44 ± 0.93 % respectively (P = 0.52). TNF-a/IL-10 (29.61 ± 2.43 vs 28.95 ±2.06, P = 0.83) and IFN-g/IL-10 (16.36 ±2.22 vs 12.61 ± 0.94, P = 0.14) producing Th1/Th2 cell ratios were comparable before and after COVID-19. Conclusions: Our findings suggest that even though patients are affected by the COVID-19 during the Omicron phase, ©2022 The Authors. American Journal of Reproductive Immunology ©2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. there were no significant flares in cellular immune responses when patients recovered from COVID-19 in not hospitalized cases.
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Objetivo: Demonstrar caso de paciente com Leucemia Linfocítica Crônica (LLC) tratado com Ibrutinibe em 1ªlinha. Material e método: Relato de caso, através de consulta de prontuário e revisão de literatura. Relato de caso: Homem, 77 anos, encaminhado para hematologista devido a linfocitose, já conhecida há mais de 10 anos, porém sem desejo de investigação, uma vez acreditando ser obrigatório a realização de estudo medular. Após cerca de um ano e meio, paciente apresentou anemia e progressão linfocitária em mais de duas vezes e em período menor de 6 meses (inicialmente com 28.224 linfócitos/mm3 e após, um máximo de 273.263/mm3). Exame de FISH evidenciou IGVH não mutado, ausência de deleção do cromossomo 17 (del17) e presença de trissomia do 12. Ao exame físico, ele não apresentou alterações, bem como linfonodomegalias, em nenhum momento do seguimento. Sintoma de astenia surgiu concomitantemente ao quadro de anemia e após constatada progressão da doença, foi optado pelo tratamento do paciente. Uma vez considerando paciente idoso e com alta carga linfoproliferativa, foi prescrito inicialmente prednisona 60 mg, alopurinol enquanto foi realizado o processo de solicitação de Ibrutinibe 420 mg diário com base no protocolo ALLIANCE A041202, levando cerca de 2 meses para ser liberado pelo convênio. Com o início do tratamento específico, o paciente apresentou resposta completa em cerca de 7 meses, sem desenvolver sinais de toxicidade ou efeitos colaterais, bem como diarreia, fibrilação atrial, infecções, eventos hemorrágicos ou artralgias. Paciente se encontra em seguimento com retornos a cada 3 meses, sem recidiva e apresentou contagem de linfócitos menor de 5000/mm3, fato que nos levou a solicitar exame de pesquisa de DRM, mesmo não sendo o objetivo deste medicamento (aguardamos este resultado). Discussão e conclusão: A LLC é uma desordem linfoproliferativa caracterizada pelo acúmulo progressivo de linfócitos que são monoclonais, sendo que os linfócitos B CD5+ sofrem transformação maligna. Acomete em maior prevalência pessoas idosas e do sexo masculino, como o paciente deste caso. O início da doença costuma ser insidioso e com sintomas não específicos, com pacientes assintomáticos. Com uma sobrevida variável, entre cerca de 2 e 20 anos, com uma taxa média de 10 anos, existem critérios bem estabelecidos para indicar o início de tratamento, dentre eles, podemos citar a duplicação de linfócitos com tempo inferior a 6 meses ou sintomas relacionados à doença. Existem diversas opções terapêuticas, dentre elas, o Ibrutinibe, uma droga oral, inibidora da tirosina quinase de Bruton, bloqueando a via de sinalização do receptor de células B, importante para a sobrevivência e proliferação dos linfócitos clonais, atualmente, em geral, com indicação em primeira linha para paciente com del17, porém conforme estudo recente, Ibrutinibe demonstrou ser superior à quimioterapia em pacientes idosos com LLC. No caso em discussão, foi optado pelo Ibrutinibe em primeira linha, pois, além de ser um paciente idoso, na ocasião da progressão da doença estávamos no início da pandemia de SARS-CoV2, momento em que havia um grande receio quanto aos possíveis eventos adversos relacionados a uma quimioterapia padrão, em especial do ponto de vista infeccioso, num paciente idoso nesse contexto da pandemia. Apesar do Ibrutinibe representar um grande avanço terapêutico, deve-se considerar a questão de custos e toxicidades possíveis, uma vez que é um tratamento contínuo a longo prazo.
ABSTRACT
A Síndrome de Richter (SR) é uma condição rara caracterizada pela transformação da leucemia linfocítica crônica (LLC) mais frequentemente em linfoma difuso de grandes células B (LDCBG);todavia, menos comumente podendo se transformar em linfoma das células do manto blastoides (LCMB). A etiologia da SR é desconhecida até o momento;ainda não foram identificadas predisposições genéticas ou uma única alteração responsável por essa transformação da LLC em LCMB. Sua incidência é rara, ocorrendo transformação de LLC em 2% a 6% dos casos, e, destes, acredita-se que ocorra em < 3% dos casos por falta de evidências na literatura. O diagnóstico é realizado pela biópsia de medula óssea, por biópsia de linfonodos alterados e pelos marcadores imunohistoquímicos. O tratamento é baseado na quimioterapia e pode-se incluir o transplante de células-tronco. Esse estudo objetiva relatar e discutir a transformação da LCC em LCMB. Visto que, apesar de sua rara incidência, possui curso agressivo e de alto grau, o diagnóstico precoce se faz necessário para melhor prognóstico do paciente. Relata-se caso de paciente masculino, 63 anos, ex-tabagista pesado, ex-etilista pesado, com diagnóstico de LLC em 2011 em tratamento. Iniciada quimioterapia com 1 ciclo de rituximab em 2017, não respondendo à terapêutica. Tentou-se terapia de resgate em 2018 com rituximab + dexametasona + ciclofosfamida, sem sucesso. Iniciado em 2019 clorambucil, com resposta por 7 ciclos. Na admissão em 2020, para acompanhamento com o serviço de hematologia em hospital geral para sequência de tratamento de LLC, paciente mostra-se refratário. À ectoscopia massa bulky em região cervical à esquerda. Exames laboratoriais mostraram anemia macrocítica, leucopenia e plaquetopenia. Exames de imagem e biópsia de medula óssea revelaram esplenomegalia, linfonodomegalia paraesofágica, retrocural, mesentérica e os seguintes marcadores bioquímicos: CD20+;PAX-5+;CD5+;ciclina+;BCL2+;Ki67+;CD43+;CD3+;SOX-11+;MUM-1+;CD23-;CD10-;BCL6-;Tdt-. Conclui-se diagnóstico de síndrome de Richter com transformação LLC para LCMB, uma rara condição potencialmente relacionada à imunossupressão provocada pela doença linfoproliferativa crônica de etiologia ainda desconhecida. A evolução do paciente à nova terapêutica, o protocolo quimioterápico R-CHOP, mostrou melhora do quadro clínico no primeiro ciclo. No ínterim até o segundo ciclo, paciente contrai SARS-CoV-2 e evolui a óbito devido à infecção.