Transplante de células da medula óssea na insuficiência cardíaca chagásica: relato da primeira experiência humana / Bone marrow cell transplantation in chagas' disease heart failure: report of the first human experience / Transplante de células de la médula ósea en la insuficiencia cardíaca de la enfermedad de chagas: relato de la Primera Experiencia Humana

FUNDAMENTO: Insuficiência cardíaca (IC) causada por Doença de Chagas (DC) é uma cardiomiopatia inflamatória progressiva que afeta milhões de pessoas na América Latina. Estudos com modelos de camundongo de IC devido à DC indicam que o transplante de células mononucleares derivadas da medula óssea (TCDMO) pode reduzir a inflamação, fibrose e melhorar a função miocárdica. OBJETIVO: O propósito desse estudo foi avaliar, pela primeira vez em seres humanos, a segurança e a eficácia de TCDMO no miocárdio de pacientes com IC devido à DC. MÉTODOS: Um total de 28 pacientes com IC devido à DC (média de idade de 52,2 ± 9,9 anos) com classe funcional NYHA III e IV foram submetidos à TCDMO através de injeção coronariana. Os efeitos na fração de ejeção do ventrículo esquerdo (FEVE), capacidade funcional, qualidade de vida, arritmias e parâmetros bioquímicos, imunológicos e neuro-humorais foram avaliados. RESULTADOS: Não houve complicações diretamente relacionadas ao procedimento. A FEVE foi 20,1 ± 6,8 por cento e 28,3 ± 7,9 por cento, p < 0,03 a nível basal e 180 dias após o procedimento, respectivamente. No mesmo período, melhoras significantes foram observadas na classe funcional NYHA (3,1 ± 0,3 para 1,8 ± 0,5; p < 0,001), qualidade de vida (50,9 ± 11,7 para 25,1 ± 15,9; p < 0,001), e no teste de caminhada de seis minutos (355 ± 136 m para 437 ± 94 m; p < 0,01). Não houve alterações nos marcadores de ativação imune ou neurohormonais. Nenhuma complicação foi registrada. CONCLUSÃO: Nossos dados sugerem que a injeção intracoronariana de células derivadas da medula óssea é segura e potencialmente efetiva em pacientes com IC devido à DC. A extensão do benefício, entretanto, parece ser discreta e precisa ser confirmada em estudos clínicos maiores, randomizados, duplo-cegos, controlados com placebo.

BACKGROUND: Heart failure due to Chagas' disease (HFCD) is a progressive inflammatory cardiomyopathy that affects millions of individuals in Latin America. Studies using mice models of HFCD indicate that bone marrow mononuclear cell transplantation (BMCT) may reduce inflammation, fibrosis, and improve myocardial function. OBJECTIVE: The purpose of this study was to evaluate, for the first time in humans, the safety and efficacy of BMCT to the myocardium of patients with HFCD. METHODS: A total of 28 HFCD patients (mean age 52.2 ± 9.9 years) with NYHA class III and IV were submitted to BMCT through intracoronary injection. Effects on the left ventricle ejection fraction (LVEF), functional capacity, quality-of-life, arrhythmias, biochemical, immunological, and neuro-humoral parameters, were evaluated. RESULTS: There were no complications directly related to the procedure. LVEF was 20.1 ± 6.8 percent and 28.3 ± 7.9 percent, p < 0.03 at baseline and 180 days after the procedure, respectively. In the same period, significant improvements were observed in the NYHA class (3.1 ± 0.3 to 1.8 ± 0.5; p < 0.001), quality-of-life (50.9 ± 11.7 to 25.1 ± 15.9; p < 0.001), and in the six-minute walking test (355 ± 136 m to 437 ± 94 m; p < 0,01). There were no changes in markers of immune or neurohormonal activation. No complications were registered. CONCLUSION: Our data suggest that the intracoronary injection of BMCT is safe and potentially effective in patients with HFCD. The extent of the benefit, however, appears to be small and needs to be confirmed in a larger randomized, double blind, placebo controlled clinical trial.

FUNDAMENTO: La insuficiencia cardíaca (IC), causada por la enfermedad de Chagas (EC), es una cardiomiopatía inflamatoria progresiva que afecta a millones de personas en Latinoamérica. Estudios con modelos experimentales de IC en razón de la EC, nos indican que el transplante de células mononucleares derivadas de la médula ósea (TCMO), puede reducir la inflamación y la fibrosis, mejorando así la función miocárdica. OBJETIVO:El objetivo de este estudio fue evaluar, por primera vez en seres humanos, la seguridad y la eficacia del TCMO en el miocardio de pacientes con IC debido a la EC. MÉTODOS:Fueron estudiados un total de 28 pacientes con IC debido a la EC (con edad promedio 52,2 ± 9,9 años), en clases funcionales III y IV (NYHA), al TCMO por medio de una inyección coronaria. Se evaluaron los efectos en la fracción de eyección del ventrículo izquierdo (FEVI), capacidad funcional, calidad de vida, arritmias y parámetros bioquímicos, inmunológicos y neurohumorales. RESULTADOS:No se registraron complicaciones relacionadas directamente con el procedimiento. La FEVI pasó de 20,1 ± 6,8 por ciento para 28,3 ± 7,9 por ciento, p < 0,03, cuando se comparó con el período basal y 180 días después del procedimiento, respectivamente. En el mismo período, también se observaron mejorías en la clase funcional NYHA promedio (3,1 ± 0,3 para 1,8 ± 0,5; p < 0,001), puntuación de calidad de vida de Minnesota (50,9 ± 11,7 para 25,1 ± 15,9; p < 0,001), y en el test de esfuerzo de seis minutos (355 ± 136 m para 437 ± 94 m; p < 0,01). No hubo alteraciones en los marcadores de activación inflamatoria o neurohormonales. Ninguna complicación fue registrada. CONCLUSIÓN:Nuestros datos sugieren que la inyección intracoronaria de las células derivadas de la médula ósea es segura y potencialmente efectiva en pacientes con IC debido a la EC. La extensión del beneficio, sin embargo, parece ser discreta, y necesita ser confirmada en los ensayos clínicos randomizados, doble ciegos, controlados con placebo.

Células natural killer e vigilância imunológica: [revisão] / Natural killer cells and immune surveillance: [review]

OBJETIVOS: Analisar a importância das células natural killer, de seus receptores killer immunoglobulin-like receptors e correspondentes genes (KIR) na vigilância imunológica do organismo contra agentes infecciosos, transplantes de células-tronco hematopoiéticas, assim como sua participação na auto-imunidade. As características e o polimorfismo dos genes e receptores KIR na população brasileira serão descritos. FONTES DOS DADOS: Livros, artigos de revisão e artigos científicos recentes são citados e listados na bibliografia. A experiência pessoal é também apresentada. SÍNTESE DOS DADOS: Identificamos o perfil de genes e haplótipos KIR na população caucasóide brasileira, sendo de importância esse conhecimento para a análise da relação desse sistema com doenças. Examinamos 116 indivíduos doadores voluntários de medula óssea, identificando-se 32 genótipos e a presença de 51 e 49 por cento de haplótipos A e B, respectivamente. Foi realizado estudo comparativo entre os nossos genótipos e os de outras populações. CONCLUSÕES: A imunidade inata é uma barreira antiinfecciosa de importância em pediatria. Ela atua de maneira independente da imunidade celular e humoral, sendo mais rápida que as demais fontes de proteção do organismo. Ao mesmo tempo, ela estimula os linfócitos T CD8 a agirem e amplificarem a rede de proteção imunológica. Entretanto, como na maioria das vezes em que a imunidade atua, ela também pode ser prejudicial, agredindo o organismo por mecanismos auto-imunes ou mesmo, na sua ausência, oferecer espaço aos agentes infecciosos para agirem de forma impune.

OBJECTIVES: To analyze the importance of natural killer cells, their killer immunoglobulin-like receptors (KIR) and genes in autoimmunity and in the immune surveillance against infectious agents and stem cells transplantation. The characteristics and polymorphisms of the KIR genes and receptors in the Brazilian population is described. SOURCES: Textbooks, review articles and recent scientific articles are cited and listed in the references. SUMMARY OF THE FINDINGS: KIR genes and haplotypes within a Brazilian Caucasian population were surveyed and analyzed to assess the future relationship of this system with diseases. Of 116 voluntary bone marrow donors, we identified 32 genotypes with frequencies of A and B haplotypes of 51 and 49 percent, respectively. A comparative analysis was performed between these genotypes and those from other populations. CONCLUSIONS: Innate immunity is an important anti-infectious barrier in newborns. It is independent of both cellular and humoral immunity, can be faster and confers great advantage in early age. At the same time, it stimulates CD8 T lymphocytes to act and amplify the immunological protection network. Nevertheless, as in the majority of situations in which immunity is activated, it can also be harmful, damaging the body through autoimmune mechanisms or even, through its absence, creating space for infectious agents to act free. Our study of a control group for KIR genotype and haplotypes in Brazilian Caucasoids could be used in future analyse of diseases related to these genes.

Trasplante de células hemopoyéticas: en los síndromes mielodisplásicos / Transplant of hemopoyetic cells: in myelodisplastic syndrome

En el presente trabajo se realizó un estudio retrospectivo de 22 pacientes diagnosticados con síndrome mielodisplásico y a los cuales se les realizó un trasplante de células hemopoyéticas con el fin de evitar el progreso de la enfermedad a un proceso mieloproliferativo. El estudio comprende el período entre octubre de 1988 y diciembre de 2005, y su objetivo es comparar los resultados y evolución de los pacientes con otros centros de trasplante. La sobrevida de nuestros pacientes es similar a la reportada en otros centros.

In the present work a retrospective study of 22 patients with myelodispastic syndrome who underwent a transplant of hemopoyetic cells in order to avoid the progression of the disease in to a myloproliferative process. The study takes into account all the data beginning October 1988 and ending December to 2005, and its objective is to compare the results and the prognosis of these patients against the results of other transplant centers. The super life of our patients is similar to the reports of other centers.

Impairment of cytomegalovirus-specific cellular immune response as a risk factor for cytomegalovirus disease in transplant recipients: [review]

Human cytomegalovirus (CMV) infection is common in most people but nearly asymptomatic in immunocompetent individuals. After primary infection the virus persists throughout life in a latent form in a variety of tissues, particularly in precursor cells of the monocytic lineage. CMV reinfection and occurrence of disease are associated with immunosuppressive conditions. Solid organ and bone marrow transplant patients are at high risk for CMV disease as they undergo immunosuppression. Antiviral treatment is effective in controlling viremia, but 10-15 percent of infected patients can experience CMV disease by the time the drug is withdrawn. In addition, long-term antiviral treatment leads to bone marrow ablation and renal toxicity. Furthermore, control of chronic CMV infection in transplant recipients appears to be dependent on the proper recovery of cellular immunity. Recent advances in the characterization of T-cell functions and identification of distinct functional signatures of T-cell viral responses have opened new perspectives for monitoring transplant individuals at risk of developing CMV disease.

Impact of cytomegalovirus and grafts versus host disease on the dynamics of CD57+CD28-CD8+ T cells after bone marrow transplant

OBJECTIVES: The present study aimed to evaluate the dynamics of CD28 and CD57 expression in CD8+ T lymphocytes during cytomegalovirus viremia in bone marrow transplant recipients. METHODS: In a prospective study, blood samples were obtained once weekly once from 33 healthy volunteers and weekly from 33 patients. To evaluate the expression of CD57 and CD28 on CD8+ T lymphocytes, flow cytometry analysis was performed on blood samples for four months after bone marrow transplant, together with cytomegalovirus antigenemia assays. RESULTS: Compared to cytomegalovirus-seronegative healthy subjects, seropositive healthy subjects demonstrated a higher percentage of CD57+ and a lower percentage of CD28+ cells (p<0.05). A linear regression model demonstrated a continuous decrease in CD28+ expression and a continuous increase in CD57+ expression after bone marrow transplant. The occurrence of cytomegalovirus antigenemia was associated with a steep drop in the percentage of CD28+ cells (5.94 percent, p<0.01) and an increase in CD57+ lymphocytes (5.60 percent, p<0.01). This cytomegalovirus-dependent effect was for the most part concentrated in the allogeneic bone marrow transplant patients. The development of acute graft versus host disease, which occurred at an earlier time than antigenemia (day 26 vs. day 56 post- bone marrow transplant), also had an impact on the CD57+ subset, triggering an increase of 4.9 percent in CD57+ lymphocytes (p<0.05). CONCLUSION: We found continuous relative changes in the CD28+ and CD57+ subsets during the first 120 days post- bone marrow transplant, as part of immune system reconstitution and maturation. A clear correlation was observed between the expansion of the CD57+CD28-CD8+ T lymphocyte subpopulation and the occurrence of graft versus host disease and cytomegalovirus viremia.

IL-2 Pathway Blocking in Combination with Anti-CD154 Synergistically Establishes Mixed Macrochimerism with Limited Dose of Bone Marrow Cells and Prolongs Skin Graft Survival in Mice

To facilitate the establishment of mixed chimerism with limited dose of bone marrow (BM) cells, and to achieve tolerance in skin graft model, combined blocking of costimulatory pathway and IL-2 pathway was used in minimally myeloablative model using busulfan. BM cells (2.5 x 10(7)) of BALB/c were injected into C57BL/6 mice at day 0 with full thickness skin graft after single dose injection of busulfan (25 mg/kg) on day-1. Recipients were grouped and injected the anti-CD154, CTLA4-Ig, anti-IL-2R at days 0, 2, 4, and 6 according to protocol. Mixed macrochimerism were induced in groups treated with anti-CD154+anti-CTLA4-Ig, anti-CD154+anti-IL-2R, and anti-CD154+anti-CTLA4 Ig+anti-IL-2R. Three groups having chimerism enjoyed prolonged graft survival more than 6 months. Superantigen deletion study revealed deletion of alloreactive T cells in combined blockade treated groups. In graft versus host disease model using CFSE staining, CD4+ T cell and CD8+ T cell proliferation were reduced in groups treated with CTLA4-Ig or anti-IL-2R or both in combination with anti-CD154. However, anti-IL-2R was not so strong as CTLA4-Ig in terms of inhibition of T cell proliferation. In conclusion, IL-2 pathway blocking combined with anti-CD154 can establish macrochimerism with limited dose of BM transplantation and induce specific tolerance to allograft.

IL-2 Pathway Blocking in Combination with Anti-CD154 Synergistically Establishes Mixed Macrochimerism with Limited Dose of Bone Marrow Cells and Prolongs Skin Graft Survival in Mice

To facilitate the establishment of mixed chimerism with limited dose of bone marrow (BM) cells, and to achieve tolerance in skin graft model, combined blocking of costimulatory pathway and IL-2 pathway was used in minimally myeloablative model using busulfan. BM cells (2.5 x 10(7)) of BALB/c were injected into C57BL/6 mice at day 0 with full thickness skin graft after single dose injection of busulfan (25 mg/kg) on day-1. Recipients were grouped and injected the anti-CD154, CTLA4-Ig, anti-IL-2R at days 0, 2, 4, and 6 according to protocol. Mixed macrochimerism were induced in groups treated with anti-CD154+anti-CTLA4-Ig, anti-CD154+anti-IL-2R, and anti-CD154+anti-CTLA4 Ig+anti-IL-2R. Three groups having chimerism enjoyed prolonged graft survival more than 6 months. Superantigen deletion study revealed deletion of alloreactive T cells in combined blockade treated groups. In graft versus host disease model using CFSE staining, CD4+ T cell and CD8+ T cell proliferation were reduced in groups treated with CTLA4-Ig or anti-IL-2R or both in combination with anti-CD154. However, anti-IL-2R was not so strong as CTLA4-Ig in terms of inhibition of T cell proliferation. In conclusion, IL-2 pathway blocking combined with anti-CD154 can establish macrochimerism with limited dose of BM transplantation and induce specific tolerance to allograft.

Avaliação da reconstituição imunológica e da resposta anti-citomegalovirus nos receptores de transplante de medula óssea / Anti-cytomegalovirus immunity reconstitution following autologous and allogeneic stem cell and bone marrow transplantation as assessed by CD8+ T cell phenotyping and function

O citomegalovírus é uma séria ameaça aos receptores de transplante de medula óssea. A reativação está associada com uma imunidade mediada por células TCD8+ defeituosa. Nosso objetivo foi correlacionar as diferentes subpopulações de células TCD8+ com a reconstituição imunológica dos pacientes, especificamente a imunidade anti-citomegalovírus, analisando as subpopulações de células T infundidas nas diferentes modalidades de transplante de medula óssea. Receptores de transplante alogênico de células tronco mobilizadas para o sangue periférico (n=16) ou coletadas diretamente da medula óssea (n=28) e receptores de transplante autólogo de células tronco mobilizadas para o sangue periférico (n=22) foram avaliados. Nós mostramos que os receptores de células mobilizadas para o sangue periférico dos doadores, tanto nos transplantes alogênicos como nos autólogos, são proporcionalmente enriquecidos por fenótipos de células memória efetora e efetora, comparada aos receptores de células procedentes diretamente da medula óssea. Este maior número das subpopulações de células TCD8+ mais diferenciadas foi também correlacionado com maior número de células contendo altos níveis de granzima B, a qual é um outro marcador de valor dos linfócitos citotóxicos, sendo mais evidente nos receptores de transplante autólogo. Ao mesmo tempo, eles apresentaram menos freqüentemente reativação pelo citomegalovírus, e mais freqüentemente produziram interferon-gama em resposta ao antígeno do citomegalovírus / Cytomegalovirus is a serious threat to the recipients of bone marrow transplantation. Reactivation is associated with defective CD8+ T cell-mediated immunity. We aimed to correlate the different subsets of CD8+ T cells with the patients’ immune reconstitution, specifically anti CMV immunity, by analyzing the CD8+ T cell subsets infused in the different types of bone marrow transplantation. Recipients of allogeneic transplant of peripheral blood stem cells (n=16) or bone marrow (n=28) and recipients of autologous transplant of peripheral blood stem cells (n=22) were evaluated. We show that recipients of stem cells from donor’s peripheral blood, either allogeneic or autologous, are proportionally enriched for effector memory and effector phenotypes, compared to the recipients of stem cells of bone marrow origin...

Bone Marrow Transplant in Pakistan: indications and Economics

Bone marrow transplant has become the treatment of choice in a number of disease and its indications are increasing every day. Until recently as it was only available in countries abroad the cost was prohibitive. For this reason majority of patients never thought about it. The facility has now become available in Pakistan at a much lower cost. Because of the limited number of transplant beds it is important that only selected patients should be advised about it. The article reviews aspects to be considered before advising a patient to undergo bone marrow transplant

HLA and bone marrow transplant donor search strategies.

Searching for a family donor other than an HLA identical sibling can be successful. The chance of finding an identical or one antigen mismatched family donor can be calculated with a computer program, so this may help in the decision making whether to perform extended family typing or not. Extended family donors are often better matched rather than unrelated donors. The reason is that they have at least one haplotype genetically identical to the patient, and that there may be some higher match grade for the minor histocompatibility antigens. Sometimes extended family donor could be the only donor for the patient. Ethical considerations have to be taken into account and extended family donors should be volunteer donors.

Vacunación en niños receptores de trasplante de médula ósea / Immunization after bone marrow transplantation

En este artículo se hace una revisión sobre la prevención de infecciones mediante la inmunización de pacientes receptores de trasplante de médula ósea (TMO). En estos pacientes la inmunidad está afectada por factores como el tipo de trasplante (alogénico o autólogo), el desarrollo de enfermedad de injerto contra huésped y la terapia inmunosupresora. En el período tardío de recuperación post-trasplante, la medida más útil para prevenir infecciones se basa en la aplicación de vacunas. Hay un creciente número de niños sometidos a TMO que se benefician de la aplicación de vacunas como la DPT, DT, IPV, Hib, MMR, hepatitis B, neumococo, influenza y meningococo. La vacuna OPV está contraindicada en todos los pacientes inmunocomprometidos y en sus contactos en la escuela o en la familia. En general estos pacientes tienen una respuesta inmunodeficiente 12 meses después del trasplante, pero pueden vacunarse a medida que van recuperando funciones inmunes específicas. Después del trasplante, primero se recuperan las células fagocíticas y esto es seguido por una re-población de linfocitos alrededor de los 3 meses. Las inmunoglobulinas totales se recuperan entre los 4 y 12 meses, aunque la IgA y la IgG2 pueden tardar años. Un año después del trasplante se normaliza la relación de células T y la respuesta específica contra antígenos de células B. Hay que reconocer que un solo esquema para estos pacientes es una propuesta muy general por lo que idealmente cada paciente deberá valorarse en forma individual. Algunos expertos deciden inmunizar a todos los niños sin evaluación serológica y otros basan su decisión en título de anticuerpos específicos después del trasplante. De cualquier forma los receptores de TMO poseen alto riesgo de infección y al no vacunarlos se pierde un excelente recurso para su reconstitución inmune que los protege contra infecciones con elevada morbilidad y mortalidad.

Aspectos imunológicos dos transplantes de células tronco hematopoéticas / Immunological aspects of hematopoietic stem cell transplantation

A integridade funcional do sistema imunológico é vital para o sucesso das várias modalidades de transplantes de células-tronco hematopoéticas (TCTH). Nesta revisäo, discutem-se a reconstituiçäo imunológica pós-TCTH, o papel das citocinas e dos antígenos de histocompatibilidade nas complicaçöes, e nos resultados dos transplantes e o emprego dos TCTH para tratamento de deficiências imunológicas e de doenças auto-imunes.

Effects of Mixed Chimerism and Immune Modulation on GVHD, Disease Recurrence and Survival after HLA-identical Marrow Transplantation for Hematologic Malignancies

BACKGROUND: The success of allogeneic bone marrow transplantation(allo-BMT) is affected by underlying disease relapse. Although mixed chimerism(MC) is not necessarily a poor prognostic factor, several groups have suggested that MC is associated with an increased risk of disease relapse. There is evidence that patients with MC benefit from additional immunotherapy if the treatment is started in minimal residual disease status(mixed chimerism status), not in frank hematological relapse. The purposes of this study are to evaluate 1) the risk for relapse or graft rejection in correlation to persistent MC status after allo-BMT, and 2) the possibility of preventing relapse by immune modulation treatments (withdrawal or rapid taper-off of post-transplant immuno-suppression, additional interferon treatment, or the administration of donor lymphocytes) in hematologic malignancies. PATIENTS AND METHODS: Of 337 allogeneic donor-recipient pairs between March 1996 and August 1998, 12 patients who showed persistent or progressive MC and who received immune modulation treatments were evaluated. Twelve patients, median age 31 years(range 9 to 39 years), received an allo-BMT for: acute myelogenous leukemia(AML, n = 5), chronic myelogenous leukemia(CML, n = 4), acute lymphocytic leukemia(ALL, n = 3). Serial polymerase chain reaction(PCR) analysis of YNZ 22-, 33.6-minisatellites or Y chromosome-specific PCR analysis at short term intervals(pre- and post-transplant 1, 3, 6, 9, ... months) was performed. Once MC was detected, immune modulation treatments on the basis of increasing MC in an early phase of recurrence of underlying disease were started. RESULTS: Nine of 12 patients converted to complete chimerism(CC) (AML 5/5, CML 3/4, ALL 1/3). Four of 9 CC patients developed graft-versus-host disease(GVHD) grade < or = 2 during immune modulation. All were treated successfully with steroids. Three patients who were not converted to CC showed relapse of underlying diseases or graft failure. CONCLUSION: The results demonstrate that, in patients with hematologic malignancies after allo-BMT, persistent MC is associated with relapse of underlying diseases or graft failure. Furthermore, when patients receive early immune modulation treatment, MC can be changed to complete donor pattern chimerism and ultimately prevent relapse.

Calprotectina epidérmica en la reacción injerto-versus-huésped con depleción linfocitaria cutánea / Epidermal calprotectin in lymphocyte-depleted cutaneous graft-vs-host reaction

Una de las complicaciones más importantes asociada a los trasplantes de médula ósea es la Reacción Injerto versus Huésped (RIVH). Los regímenes inmunosupresores reducen la severidad de las lesiones cutáneas determinando una forma peculiar de RIVH con deplesión linfocitaria (RIVH-DL), caracterizada por pocas células inflamatorias reconocibles y casi una total ausencia de daño epidérmico. Los recientemente actualizados criterios histopatológicos para la RIVH ayudan poco para el diagnóstico de la RIVH-DL. Como la calprotectina (L1-proteína) ha sido encontrada en diversos tipos de estress epitelial, analizamos la calprotectina epitelial en la RIVH-DL. La expresión de calprotectina se estudió por inmunohistoquímica usando Mac 387 moAb en 50 casos de RIVH-DL y 40 casos de reacciones tóxicas secundarias a los regímenes condicionantes pre-trasplante o por drogas post-trasplante. Se detectó calprotectina en queratinocitos de apariencia normal en todos los casos de RIVH-DL y en la mayoría de las dermatitis con citotoxicidad inducidas por drogas. Concluímos que la inmunoreactividad a la calprotectina aparenta ser una clave diagnóstica para la RVIH-DL. Se expresión aparece precozmente en el curso de la RIVH-DL independientemente del grado histológico de la reacción. Sin embargo, no puede ser usada en forma aislada para distinguir entre una RIVH-DL inicial y una dermatitis inducida por drogas

Avaliaçäo da síntese intratecal de imunoglobulinas no transplant de medula óssea / Immunoglobulins intrathecal synthesis evaluation in bone marrow transplantaion

O envolvimento da doença do enxerto contra o hospedeiro crônica (DECH-C) no sistema nervoso central tem sido especulado. Há uma série de semelhanças clínicas e fisiopatológicas entre DECH-C e doenças auto-imunes, o que leva a questionar sobre a síntese intratecal de imunoglobulinas. Este estudo avalia esta síntese, em particular durante a DECH-C, de forma quantitativa, a fim de observar sua incidência e possível fisiopatologia. Foram estudadas amostras pareadas de LCR e soro de 33 pacientes com leucemia mielóide crônica submetidos a transplante de medula óssea (TMO) alogênico, com doador aparentado, HLA idêntico. As amostras foram coletadas nos períodos pré TMO, pós TMO e concomitante à DECH-C. Näo foi evidenciada produçäo intratecal de IgG ou IgA nas várias fases do TMO. Apenas casos isolados evidenciaram síntese, inclusive de IgM, durante a DECH-C.

Paciente com olho seco pós-transplante de medula óssea: relato de caso / Dry eye after bone marrow transplantation

Os autores descrevem um caso de olho seco pós-transplante de medula óssea associado a lesäo corneana peresistente. Discutem a possibilidade de correlaçäo entre os achados de auto-anticorpos séricos contra constituintes celulares de córnea e conjuntiva presentes neste paciente, e a patogênese da ceratoconjuntivite sicca pós-transplante de medula óssea