Depleción de eosinófilos: muchas implicaciones en modelos múridos, pocas estudiadas en humanos / Eosinophil depletion: many implications in murine models, few studied in humans

The eosinophil is a cell of the immune system, with an arsenal of substances that can alter the balance that exists in the different organs where they are found. With the advent of monoclonal antibodies, concern about their depletion has become an important turning point in their formulation. For this reason, it is of vital importance to investigate the consequences of the mechanism of action of biological agents, in the short and long term. This review tries to show the role of eosinophils in both homeostasis and disease, and their relationship and interaction with monoclonal drugs in diseases focused on the Th2 profile. It is expected that this article can be useful when making the decision to start treatment with monoclonals, specifically anti-interleukin-5 or against its receptor

Acute radiation syndrome in a non-destructive testing worker: a case report

BACKGROUND: In Korea, there were repeated radiation exposure accidents among non-destructive testing workers. Most of the cases involved local injury, such as radiation burns or hematopoietic cancer. Herein, we report a case of acute radiation syndrome caused by short periods of high exposure to ionizing radiation. CASE PRESENTATION: In January 2017, Korea Information System on Occupational Exposure (KISOE) found that a 31-year-old man who had worked in a non-destructive testing company had been overexposed to radiation. The patient complained of symptoms of anorexia, general weakness, prostration, and mild dizziness for several days. He was anemic. The venous injection areas had bruises and bleeding tendency. Blood and bone marrow testing showed pancytopenia and the patient was diagnosed with acute radiation syndrome (white blood cells: 1400/cubic mm, hemoglobin: 7.1 g/dL, platelets: 14000/cubic mm). He was immediately prohibited from working and blood transfusion was commenced. The patient’s radiation exposure dose was over 1.4 Gy (95% confidence limits: 1.1–1.6) in lymphocyte depletion kinetics. It was revealed that the patient had been performing non-destructive tests without radiation shielding when working in high places of the large pipe surface. CONCLUSIONS: Exposure prevention is clearly possible in radiation-exposed workers. Strict legal amendments to safety procedures are essential to prevent repeated radiation exposure accidents.

Evaluation of thymic lymphocyte loss of broiler using Digital Analysis of the Lymphoid Depletion System (ADDL) / Avaliação de perda de linfócitos do timo em frangos usando análise digital do sistema de depleção linfóide (ADDL)

The thymus is a lymphoid organ and usually evaluated for the degree of lymphocyte loss with subjective histological techniques. This study aimed to adapt and to apply of the digital analysis of the lymphoid depletion system (ADDL) in the thymus in order to obtain a more accurate analysis. Glucocorticoid was used to induce immunosuppression in 55 broilers at 21 days of age; other 15 broilers were the control group. After euthanasia of the broilers, postmortem examination was made. Both thymic chains were collected and six lobes were selected for histological examination of the degree of lymphocyte depletion (scores 1 to 5) and for submission to all stages of processing by the ADDL system. The artificial constructed neural networks (ANN) obtained 94.03% of correct classifications. In conclusion, it was possible to adopt objective criteria to evaluate thymic lymphoid depletion with the ADDL system.(AU)

O timo é um órgão linfóide, que é normalmente avaliado para o grau de perda de linfócitos a partir de técnicas histológicas subjetivas. Este trabalho teve como objetivo a adaptação e aplicação do sistema de análise digital de depleção linfóide (ADDL) para o timo, a fim de tornar sua análise mais acurada. Glicocorticóides foram utilizados a fim de induzir imunossupressão em 55 aves de 21 dias de idade. Outras 15 aves formaram o grupo controle. Posteriormente, para cada um dos aves, realizou-se a eutanásia e necropsia. Ambas as cadeias do timo foram coletadas e foram selecionadas seis lóbulos para processamento histológico, análise quanto ao grau de depleção linfocitária (escores de 1-5) e submissão a todas as fases do processamento pelo sistema ADDL. Observou-se que a rede neural artificial (RNA) construída obteve 94,03% de classificações corretas. Em conclusão, foi possível adotar critérios objetivos para avaliar a depleção linfóide tímica utilizando o sistema ADDL.(AU)

Evaluation of bursal lymphoid depletion: comparison between the conventional histology method and digital lymphocyte depletion evaluation system / Avaliação da depleção linfóide bursal: comparação entre a histologia convencional e o sistema de avaliação digital da depleção linfocitária

Fifty-five bursa of Fabricius (BF) were evaluated by optical microscopy for three different avian histopathologists (H1, H3 and H4) to determine the degree of lymphoid depletion. One histologist evaluated the same slides at two different times (H1 and H2) with four-months interval between the observations. The same BFs were evaluated using the system of Digital Lymphocyte Depletion Evaluation (ADDL), being performed by three differents operators of the system, not histopathologists. The results showed was a significant difference between the histopathologists and between the scores established by the same expert (H1 and H2). However, there were not significant differences between the scores with the ADDL system, obtained using ADDL. The results make clear the fragility of the subjective lymphocyte depletion score classification by the traditional histologic method, while the ADDL system proves to be more appropriated for the assessment of the lymphoid loss in the BF.(AU)

Cinquenta e cinco bursas de Fabricius (BF) foram avaliadas através da microscopia óptica por três diferentes histopatologistas aviários (H1, H3 e H4) para determinar o grau de depleção linfóide. Um histopatologista avaliou as amostras em dois momentos distintos (H1 e H2) com quatro meses de intervalo entre as observações. As mesmas BF foram avaliadas utilizando-se o sistema de Avaliação Digital da Depleção Linfocitária (ADDL), sendo realizadas por três diferentes operadores do sistema, não histopatologistas. Os resultados mostraram diferenças significativas entre os histopatologistas e entre um mesmo histopatologista (H1 e H2). Contudo, não houve diferenças significativas entre os escores obtidos utilizando-se ADDL. Estes resultados caracterizam a fragilidade da classificação subjetiva em escores de depleção linfóide, enquanto o sistema ADDL prova ser um sistema robusto de avaliação da perda linfocitária na BF.(AU)

The kinetics and prognosis of platelet reconstitution after unmanipulated haploidentical stem cell transplantation without in vitro T cell depletion / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the kinetics of platelet reconstitution and its prognostic significance in patients received unmanipulated haploidentical stem cell transplantation (Haplo-HSCT) without in vitro T cell depletion.</p><p><b>METHODS</b>A total of 291 patients received Haplo-HSCT without in vitro T cell depletion between January 2007 to December 2008 were retrospectively reviewed. They were categorized into 3 groups according to the platelet count on day 30, day 60 and day 90: (1) persistent thrombocytopenia (Group A) was defined as the platelet count never reached 50×10⁹/L on the three time points; (2) unstable thrombocytopenia (Group B): the platelet count recovered to a level of 50×10⁹/L by day 30 or 60 or 90, yet did not reach a level of more than 100×10⁹/L; (3) non-thrombocytopenia (Group C): the platelet count was higher than 100×10⁹/L on day 90. The kinetics of platelet reconstitution, overall survival (OS) and treatment related mortality (TRM) were compared between 3 groups.</p><p><b>RESULTS</b>Of the 291 consecutive patients, 288 cases engrafted successfully and 262 cases were platelet transfusion independent. The median intervals of neutrophil and platelet engraftment were 13 (9-29) days and 17 (7-180) days, respectively. The cumulative incidence of grade III-IV acute graft versus host disease (GVHD) on day 100 and chronic GVHD at 3 years were 14.7% and 56.4% respectively. OS and TRM at 3 years were 64.6% and 22.3% respectively. At the end of the follow-up, 266 cases were platelet transfusion independent: including 71 (24.4%) cases in Group A, 147 (50.5%) in Group B and 73 (25.1%) in Group C. OS in group A, B and C was 38.0%, 69.4% and 80.8% (P<0.05) respectively. TRM in Group A, B and C was 53.5%, 17.7% and 1.4% (P<0.05) respectively. Persistent thrombocytopenia was related with lower OS and higher TRM in multivariate analysis.</p><p><b>CONCLUSION</b>Persistent thrombocytopenia was common after Haplo-HSCT without in vitro T cell depletion, and patients with persistent thrombocytopenia have poor OS and higher TRM.</p>

Linfoma de Hodgkin con depleción linfocítica e infiltración difusa de médula ósea / Hodgkin's lymphoma with lymphocyte depletion and diffuse bone marrow infiltration

Se presenta el caso clínico de un paciente varón de 38 años de edad, agricultor, natural de Lamas, San Martín (selva peruana), quien desde hacía 8 meses presentaba diarreas, fiebre intermitente, dolor abdominal, pérdida ponderal y anemia severa. Aunque lúcido, a su ingreso el paciente exhibía mal estado general, palidez y adenopatías generalizadas de menos de 0,5 cm, hepatoesplenomegalia y matidez desplazable. La tomografía computarizada abdominal reveló hepatoesplenomegalia y múltiples adenopatías retroperitoneales, mesentéricas y otras. La biopsia de ganglio mostró células de Reed Sternberg, células mononucleares, eosinófilos y escasos linfocitos. La inmunohistoquímica ganglionar fue positiva para anticuerpos CD15 y CD30. La biopsia de hueso señaló fibrosis difusa, células mononucleares y marcada escasez de linfocitos. La hibridización in situ para EBV-virus de Epstein Barr fue positiva en las células neoplásicas.

We present the case of a 38 year-old male, farmer, born in Lamas, San Martin (Peruvian jungle), who for the past 8 months suffered of diarrhea, intermittent fever, abdominal pain, weight loss and severe anemia. On admission the patient was lucid and exhibited malaise, pallor and generalized lymphadenopathy (size less than 0.5 cm) hepatosplenomegaly and abdominal displaceable dullness. Abdominal computed tomography showed hepatosplenomegaly and retroperitoneal, mesenteric and other adenopathies. Node biopsy revealed Reed-Sternberg cells, mononuclear cells, eosinophiles and scarce lymphocytes. Immunohistochemical node staining was positive for CD15 and CD30 antibodies. Bone biopsy showed diffuse fibrosis, mononuclear cells and scarcity of lymphocytes. In situ hybridization for EBV Epstein Barr virus was positive in neoplastic cells.

Pathologic Characteristics and Differential Diagnosis of Hodgkin Lymphoma / 대한내과학회지

Recent advances in the understanding of the biology of Hodgkin lymphoma have led to a new classification. Hodgkin lymphoma is now recognized as a B-cell disorder of germinal center or post-germinal center origin. In the WHO classification, Hodgkin lymphoma consists of two categories, namely, nodular lymphocyte predominant Hodgkin lymphoma and classical Hodgkin lymphoma. Classical Hodgkin lymphoma encompasses not only nodular sclerosis, mixed cellularity, and lymphocyte depletion subtypes, but also lymphocyte-rich subtype, among which, nodular sclerosis stands out as a distinct entity. A borderline neoplasm with features intermediate between Hodgkin lymphoma and diffuse large B-cell lymphoma has also been recognized.

Evaluation of follicular lymphoid depletion in the Bursa of Fabricius: an alternative methodology using digital image analysis and artificial neural networks / Avaliação da depleção linfóide folicular da Bursa de Fabricius: uma metodologia alternativa utilizando análise digital de imagem e redes neurais artificiais

Fifty Bursa of Fabricius (BF) were examined by conventional optical microscopy and digital images were acquired and processed using Matlab® 6.5 software. The Artificial Neuronal Network (ANN) was generated using Neuroshell® Classifier software and the optical and digital data were compared. The ANN was able to make a comparable classification of digital and optical scores. The use of ANN was able to classify correctly the majority of the follicles, reaching sensibility and specificity of 89 percent and 96 percent, respectively. When the follicles were scored and grouped in a binary fashion the sensibility increased to 90 percent and obtained the maximum value for the specificity of 92 percent. These results demonstrate that the use of digital image analysis and ANN is a useful tool for the pathological classification of the BF lymphoid depletion. In addition it provides objective results that allow measuring the dimension of the error in the diagnosis and classification therefore making comparison between databases feasible.

Cinquenta Bursa de Fabrícius (BF) foram examinadas através de microscopia óptica convencional e imagens digitais foram obtidas e processadas através do software Matlab® 6.5. Redes Neurais Artificiais (ANN) foram geradas com a utilização do software Neuroshell® Classifier, e os dados das análises óptica e digital foram comparados. A ANN classificou corretamente a maioria dos folículos, atingindo sensibilidade e especificidade de 89 por cento e 96 por cento, respectivamente. Quando os folículos foram agrupados de forma binária houve um aumento da sensibilidade para 90 por cento e obteve-se um valor máximo para a especificidade de 92 por cento. Estes resultados demonstram que o uso da análise digital de imagem associada à ANNé uma ferramenta bastante útil para a classificação patológica da depleção linfóide da BF. Além disso, fornece resultados objetivos que permitem medir a dimensão do erro classificatório, tornando possível a comparação entre distintos bancos de dados.

Recaída sistémica con compromiso de SNC de linfoma Hodgkin y respuesta al esquema Gemcitabina/Vinorelbina / Systemic Relapse with involvement of the CNS by Hodgkin's Lymphoma: response to gemcitabine/Vinorelbine Scheme

El compromiso del sistema nervioso central (SNC) por Linfoma de Hodgkin es infrecuente. El tratamiento con Gemcitabina/Vinorelbina es efectivo y bien tolerado en pacientes con Linforma de Hodkgin recaídos/refractarios.

Central nervous system involvement by Hodgkin is rare. Gemcitabine/Vinorelbine is an effective and well tolerated regimen for patients with relapsed and refractory Hodgkin's lymphoma.

Anemia y depleción de las reservas de hierro en niños con síndrome de down / Anemia y iron stores depletion in children with down syndrome

En el Síndrome de Down (SD) son escasos los estudios que determinan la prevalencia de anemia y deplecion de las reservas de hierro (DRFe). Evaluar la prevalencia de anemia y DRFe en ninos con SD de Maracaibo-Venezuela. Se realizó un estudio descriptivo en 169 ninos entre 4-14 años: ochenta y siete sin SD y 80 con SD, sin procesos infecciosos e inflamatorios activos. Se consideró anemia valores de hemoglobina <110 g/L en <5 años, <115 g/L entre 5-11 años y <120 g/L entre 12-14 años. Microcitosis vcm<80 fL, Hipocromía HCM<27 pg. Se consideró DRFe=ferritina<15µg/L; riesgo de DRFe (RDRFe) ferritina=15-20µg/L y reservas normales (RFe normal) ferritina>20µg/L. Los datos fueron analizados con el pregrama de estadísticas SAS, y se consideró como significación estadística una p<0,05. La prevalencia total de anemia fue 20,71 por ciento, significativamente más baja en niños con SD (5,92 por ciento) (p<0,01). La prevalencia de microcitosis (5,0 por ciento) e hipocromia (18,75 por ciento) también fue menor en estos niños (p<0,0001), no observándose casos de macrocitosis, pero si de hipercromía (7,50 por ciento). La prevalencia de DRFe en niños con SD (9,14 por ciento) fue superior a la observada en niños sin SD; sin embargo, la prevalencia de RDRFe (36,59 por ciento), fue más baja en niños con SD. No se observaron diferencias estadísticamente significativas en cuanto a edad, peso y estatura. La depleción y riesgo de depleción de las reservas de hierro son deficiencias nutricionales prevalentes en niños con Síndrome de Down, que requieren de una atención especial del estado nutricional y de salud en esta población.

There are few studies in relation to the prevalence of anemia and depletion of iron stores (DIS) in individuals with Down Syndrome (DS). To evaluate the prevalence of anemia and DIS in children with Down Syndrome from Maracaibo-Venezuela. A descriptive study was carried out on 169 chidren (aged 4 to 14 years); 87 without DS and 80 with DS; without infectious or inflammatory processes. Anemia was considered when Hemoglobin <110 g/L in <5y old, Hb<115 g/L in 5 to 11y old and Hb<120 g/L in 12 to 14 y old; microcytosis (mean corpuscular volume MCV<80 fL) and hypochromia (Mean Corpuscular Haemoglobin MCH<27 pg). DIS=ferritin<15µg/L; DIS risk ferritin=15-20µg/L and normal iron stores normal (NIS) ferritin>20µg/L. Statistical analysis was performed with SAS programs, Statistical significance was considered when p<0.05. The overall prevalence of anemia was 20.71%. This prevalence was much lower in children with DS (5.92%; p<0.01) Prevalence of microcytosis (5.0%) and hypochromia (18.75%) were also significantly lower in children with DS (p<0.0001). No macrocytosis was observed but hipercromia was detected in 7.50%. Although, the prevalence of DIS (9.14%) was higher in children with DS, the prevalence of DIS risk was lower (36.59%). Age, weight and height did not show statistical differences between groups. DIS and DIS risk are prevalent nutritional deficiencies in children with Down Syndrome, which require special attention in order to improve nutritional and health status in this population.

Presença de aditivos conservantes (nitrito e sulfito) em carnes bovinas moídas, comercializadas em mercados varejistas / Presence of additive conserving (nitrite and sulphite) in grounded beef, commercialized in the retail markets

No presente trabalho, objetivou-se avaliar a prática fraudulenta da adição de nitrito e sulfito, e parâmetros físico-químicos de qualidade em carnes bovinas moídas in natura e resfriadas, comercializadas em mercados varejistas do estado do Rio de Janeiro. Avaliou-se também o grau de depleção do nitrito pós-cocção. Os resultados obtidos demonstraram que de 35 amostras analisadas, 37,14% apresentaram nitrito, 11,42% sulfito, 17,14% amônia e 17,14% odor desagradável na prova da cocção. Todas as amostras apresentaram o valor de pH dentro do padrão oficial. A maior concentração de nitrito detectada foi 1,17mg.Kg-1 e a menor 0,173 mg.Kg-1. Após cozimento de amostras onde se detectou nitrito, houve depleção significativa desta substância. A detecção de nitrito e sulfito em carnes in natura além de caracterizar o descumprimento da legislação vigente por parte dos comerciantes, pode representar um risco à saúde da população, devido ao potencial tóxico destas substâncias quando ingeridas em excesso.

So, the present work aims to evaluate the quality physiochemical parameters as well as the nitrite and sulphite fraudulent addition to “in natura” grounded beef which was cooled commercialized in the State of Rio retail markets. The nitrite depletion degree after cooking was also evaluated. Our results have demonstrated that in 35 analyzed samples, 37.14% presented sodium nitrite while 11.42% sulphite, 17.14% ammonia and 17.14% unpleasant smell at cooking test. All the samples presented standard pH value. 1.17 mg.Kg-1 and 0.173 mg.Kg-1 were the highest and the lowest nitrite concentration detected, respectively. We found significant depletion of the nitrite after cookihg the samples with this substance. The detention of nitrite and sulfite in meats “in natura” characterizes the disobedience of the current law. The addition of these substances can represent a risk to the health of the population. They are potentially toxic substances when ingested in excess.

An effective method for T-cell and B-cell simultaneous depletion in vitro from mobilized peripheral blood stem/progenitor cell graft for haploidentical transplantation / 中国实验血液学杂志

Depletion of T and B cells from the graft is prerequisite for haploidentical transplantation to decrease the risk of GVHD and EBV-associated lymphoproliferative disease. This study was aimed to investigate the performance of T-cell and B-cell simultaneous depletion from mobilized peripheral blood stem cells (PBSCs) for the first time in China, using anti-CD3 and anti-CD19 antibodies conjugated to magnetic microbeads by the CliniMACS device. The depletion efficiency of T-cell and B-cells was analyzed by flow cytometry; the function of the stem cells after depletion was evaluated using colony assays. The results indicated that the mononuclear cell count prior to T- and B-cell depletion was 4.88 x 10(10). After depletion, the percentage of T cells was 0.02% with a log (10) depletion of 4.4. The percentage of B cells was less than 0.01% with a log (10) depletion of at least 3.3. The product contained not only CD34(+) stem cells, but also NK cells, monocytes and granulocytes. After T- and B-cell depletion the purity of CD34(+) cells was 0.98%, the number of CD34 cells was 1.84 x 10(8) and their recovery rate was 69.7%. The number of NK cells was 2.54 x 10(9) and the recovery rate of NK cells was 71.7%. In vitro colony assays showed no negative impact on function of the hematopoietic stem cells. In conclusion, the CliniMACS system can be used to efficiently deplete T and B cells from PBSCs simultaneously, without adverse effect on biological function of hematopoietic stem cells. This study provides technical platform for haploidentical hematopoietic stem cell transplantation.

Selective elimination of alloreactive donor lymphocytes by using TBI and cyclophosphamide / 中国实验血液学杂志

This study was aimed to investigate a new method of avoiding graft-vs-host disease (GVHD) through selective elimination of alloreactive donor lymphocytes by using total body irradiation (TBI) and cyclophosphamide (Cy). Female (BALB/c x C57BL/6) F1 mice (H-2(d/b)) as recipients received (60)Co gamma-ray sublethal TBI of 4 Gy on day 0 followed by being inoculated with P388D1 leukemia cell line on day 1, injection of allogeneic splenocytes from C57BL/6 male mice (H-2(b)) was carried out for induction of graft-vs-leukemia (GVL) effect prior to stem cell transplantation (SCT), intraperitoneally injection of cyclophosphamide (Cy) (200 mg/kg) and TBI (9 Gy) was given on day 6. One day later, treated mice were rescued with bone marrow hematopoietic stem cells from (BALB/c x C57BL/6) F1 male mice (H-2(d/b)). The results showed that recipients had no occurrence of leukemia and GVHD through selective elimination of alloreactive donor lymphocytes by Cy and TBI, survived more than 210 days, the complete-donor chimerism occurred on day 21 after transplantation. The ratio of chimerism descended subsequently, but still displayed mixed-chimerism at 90 days. Control mice died of GVHD, leukemia or other death-related-transplantation within 20 to 36 days (P<0.01). It is concluded that to induce GVL effects by MHC mismatched splenocytes given before syngeneic bone marrow transplantation followed by selective elimination of alloreactive donor lymphocytes through TBI and Cy, graft-vs-host disease was thus avoided.

Plasmodium berghei ANKA infection induces thymocyte apoptosis and thymocyte depletion in CBA mice

Immune responses to malaria infections are characterized by strong T and B cell activation, which, in addition of potentially causing immunopathology, are of poor efficacy against the infection. It is possible that the thymus is involved in the origin of immunopathological reactions and a target during malaria infections. This work was developed in an attempt to further clarify these points. We studied the sequential changes in the thymus of CBA mice infected with Plasmodium berghei ANKA, a model in which 60-90 percent of the infected animals develop cerebral malaria. During the acute phase of infection, different degrees of thymocyte apoptosis were recorded: (1) starry-sky pattern of diffuse apoptosis with maintenance of cortical-medullary structure; (2) intense apoptosis with cortical atrophy, with absence of large cells; (3) severe cortical thymocyte depletion, resulting in cortical-medullary inversion. In the latter, only residual clusters of small thymocytes were observed within the framework of epithelial cells. The intensity of thymus alterations could not be associated with the degree of parasitemia, the expression of clinical signs of cerebral malaria or intensity of brain lesions. The implications of these events for malaria immunity and pathology are discussed.

Profound peripheral T-lymphocyte depletion and activation in disseminated tuberculosis

Three HIV-1-seronegative patients with disseminated tuberculosis presented significant depletion of T-cell counts, in CD4+ and/or CD8+ cells, associated with increased expression of activation marker CD38 on CD8+ T-lymphocytes. This finding raises the question of potential mechanisms involved in the activation or loss of T-cells in disseminated tuberculosis.

Role of alloreactive natural killer cell in mouse MHC haploidentical bone marrow transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the effect of alloreactive natural killer (NK) cells used in conditioning regimen on elimination of recipient-type T cell and granulocyte, reconstitution of hematopoiesis, engraftment and graft-versus-host disease (GVHD) in murine major histocompatibility complex (MHC) haploidentical bone marrow transplantation (BMT).</p><p><b>METHODS</b>The murine model of MHC haploidentical BMT was established by using (C57BL/6 x BALB/c) BCF(1) (H-2(d/b)) mouse as the donor, and BALB/c (H-2(d)) mouse as the recipient. Recipient mice were divided into 8.5 Gy control group and 7, 6 and 5 Gy experimental groups according to different irradiation dose and different kinds of NK cell treatment. The control group was further subdivided into untreated and BMT groups, while each experimental group was subdivided respectively into untreated group, BMT group, non-allo-reactive NK cells (non-allo NK) group and alloreactive NK cells (allo NK) group. The effect of adding alloreactive NK cell to conditioning regimen was assessed by peripheral white blood cell and platelet counts, recipient type H-2(d+) T cells and granulocytes counts, expression of H-2(d/b+) cells and pathohistological examination.</p><p><b>RESULTS</b>Survival time was (6.00 +/- 0.82) days for 8.5 Gy untreated group, and beyond 60 days for all the other groups. No clinical and histopathological evidence of GVHD was observed in all the groups. The reconstitution of hematopoiesis was faster in allo NK groups than in other groups (P < 0.05). On day 1 after BMT, in allo NK groups with different irradiation dose, bone marrow and spleen recipient type H-2(d+) granulocytes and T cells were significantly decreased compared with identical BMT groups and non-allo NK groups (P < 0.05). The engraftment rates of H-2(d/b+) cells were significantly higher in 7, 6 and 5 Gy allo NK groups than in identical BMT groups and non-allo NK groups (P < 0.05, respectively).</p><p><b>CONCLUSIONS</b>In mouse MHC haploidentical BMT, alloreactive NK cell can eliminate recipient-type T cell and granulocyte, promote reconstitution of hematopoiesis, enhance engraftment while not induce GVHD.</p>

Two-signal blockade with anti-CD45RB and anti-CD154 monoclonal antibodies inhibits graft rejection via CD4-dependent mechanisms in allogeneic skin transplantation

Blockade of signal 1 or 2 for T-cell activation by the use of anti-CD45RB and anti-CD154 monoclonal antibodies (mAb) (two-signal blockade) has been proven effective in preventing or delaying graft rejection. However, the mechanisms of its immunomodulatory effects are clearly unknown and the present studies were performed to determine how the two-signal blockade modulate allogeneic immune responses, especially T-cell mediated cellular immunity, in a murine skin allograft model. We now report on the profound inhibition of alloreactive T cells by two-signal blockade via CD4-dependent mechanisms. C57BL/6 mice of BALB/c skin allograft were treated with anti-CD45RB, anti-CD154, CTLA4-Ig, or their combinations. For depletion of CD4 or CD8 T cells, the recipients received CD4-depleting or CD8-depleting mAb. We confirmed that survival of skin allograft was markedly prolongated in the two-signal blockade-treated group. In depletion study, anti-CD45RB, anti-CD154 and CD4-depleting mAb-treated group showed acute rejection of skin allograft in contrast to CD8-depleting group treated with the two-signal blockade. In the group treated with the two-signal blockade, the proportions of CD4+CD45RB(low)and CD8+CTLA-4 regulatory T cells were increased while effector CD8+ T cells, including IFN-gamma-secreting and CD8+CD62L(low)T cells, were decreased when compared with non-treated group. In contrast, the CD4-depleted group treated with the two-signal blockade resulted in recovery from immunoregulatory effects of two-signal blockade. In addition, results of IL-4 and IL-10 production were also showed CD4-dependence. Therefore, the two-signal blockade is accompanied by CD4-dependent mechanisms in allogeneic skin transplantation.

Trasplante de células progenitoras hematopoyéticas en pediatría: Una alternativa de tratamiento en inmunodeficiencias primarias / Hematopoietic stem cell transplant in combined immunodeficiency syndromes of childhood: An optimal treatment for primary immunodeficiency

The congenital immunodeficiency disorders in which the defect has been clearly traced to the stem cell can be cured with allogeneic stem-cell transplantation (SCT) from an unaffected donor. Widespread application of this treatment modality has been tempered by the fact that risk-benefit considerations do not always favor a procedure that carries a significant risk for morbidity and mortality. Some malignant disorders of childhood eventually have to be treated by an autologous or allogeneic SCT, however nonmalignant disorders can also be treated with this approach. This article reviews the current status of SCT for nonmalignant inherited immunodeficiency disorders.

Tradicionalmente el trasplante de células progenituras hematopoyéticas (TCPH) se ha utilizado en pacientes pediátricos para el tratamiento de padecimientos malignos. Sin embargo, también existen indicaciones y experiencia para padecimientos benignos dentro de los cuales se encuentran los síndromes de inmunodeficiencia combinada primaria. Estos síndromes de la infancia constituyen una serie de padecimientos que aun cuando son infrecuentes en la patología infantil constituyen un grupo de alteraciones que hasta hace más de tres décadas eran irremediablemente fatales. Con el advenimiento del TCPH el pronóstico de estos síndromes ha mejorado sustancialmente, por lo que es importante conocer sus resultados, así como su morbimortalidad asociada.

Rituximab Treatment for the Patient with Refractory Lupus Nephritis / 대한류마티스학회지

OBJECTIVE: To determine preliminary evidence for the safety and efficacy of B lymphocyte depletion therapy in refractory systemic lupus erythematosus (SLE). METHODS: Four female lupus nephritis patients who had been refractory to steroid and one or more immunosuppressive therapy were treated on an open-label basis. During a 4-week period, each patient received two 500-mg infusions of rituximab and two 750-mg infusions of cyclophosphamide. RESULTS: Patient 1, 2, and 3 were responded with rituximab treatment with improvements in SLEDAI and laboratory parameters such as C3/C4 and 24 hour urine protein. However, patient 4 had not improved with rituximab. The variation in the level of anti-double-stranded DNA antibody was different in individual patients. No significant adverse events were observed during follow-up. CONCLUSION: This study provides an evidence for the safety and possible efficacy of B lymphocyte depletion therapy in refractory lupus nephritis. However a further randomized trial is needed to confirm the efficacy and durability of remission.