Trasplante pulmonar: una perspectiva desde la inmunología / Lung transplantation: a perspective from immunology

Resumen El trasplante pulmonar implica una serie de desafíos, que como lo ha demostrado la historia, no sólo depende de un adecuado desarrollo de técnicas quirúrgicas, sino también de la comprensión de una serie de complejas interacciones inmunológicas celulares y humorales que serán las responsables del tipo de respuesta (innata y/o adquirida) fisiológica y que pudiesen desencadenar las complicaciones asociadas al trasplante (rechazo hiperagudo, agudo o crónico). Cada una de las cuales tiene su potencial prevención y/o tratamiento. El poder conocer esta serie de respuestas, permite al clínico anticiparse a algunos de estos eventos y evitar de mejor forma el daño y las consecuencias que pueden producir en los casos de trasplante pulmonar.

Lung transplantation involves a series of challenges, which as history has shown, depends not only on an adequate development of surgical techniques, but also on the understanding of a series of complex cellular and humoral immunological interactions that will be responsible for the type of physiological response (innate - acquired) and that could trigger the complications associated with transplantation (hyperacute, acute or chronic rejection). Each of which has its potential prevention and treatment. Being able to know this series of responses, allows the clinician to anticipate some of these events and to avoid in a better way the damage and the consequences that can occur in cases of lung transplantation.

Seguimiento inmunológico con anticuerpos anti-HLA por tecnología Luminex™, ¿se puede prevenir el rechazo agudo celular y humoral en trasplante de intestino? / Anti-HLA antibody immunological follow up by the Luminex TM. Is it possible to prevent the acute cell and humoral immune rejection in small bowel transplant? Report of one case

Introducción. El trasplante de intestino mejora la supervivencia de pacientes con falla intestinal secundaria al síndrome de intestino corto. Estos receptores tienen gran riesgo de rechazo agudo, por lo cual, de manera protocolaria y como método de referencia, se practican biopsias intestinales. En este reporte de caso se hizo el seguimiento inmunológico de anticuerpos anti-HLA por tecnología Luminex™ (LSA) de un paciente con trasplante de intestino más biopsias por protocolo para un diagnóstico temprano, y una adecuada correlación histológica. Presentación del caso. Se trata de un paciente de 20 años de edad con síndrome de intestino corto, que ingresó a la Fundación Valle del Lili (Cali, Colombia) y requirió un trasplante aislado de intestino. El seguimiento inmunológico se hizo con tecnología Luminex™ y biopsias intestinales mensuales. Según la tamización contemplada en el protocolo previo al trasplante, el paciente tuvo anticuerpos anti-HLA (PRA de clase I y II) negativos; y a los 11 meses después del trasplante, los anticuerpos anti-HLA de clase I y II fueron positivos. Con la prueba de LSA se detectó un anticuerpo específico contra donantes (Donor Specific Antibodies, DSA) y varios anticuerpos contra otros subtipos moleculares. Se tomó una biopsia que mostró un leve rechazo celular agudo y se inició tratamiento con plasmaféresis. Hasta 21 meses después del trasplante, el paciente no ha presentado rechazos clínicos y ha tenido una adecuada evolución clínica y paraclínica Conclusión. Este es el primer trasplante de intestino en nuestro centro, en el que se hace seguimiento inmunológico con tecnología Luminex™. Consideramos que la detección con DSA es un buen marcador de rechazo agudo humoral, que permitiría una aproximación diagnóstica y una intervención oportuna

Background: Small bowel transplant improves survival of the recipients that have intestinal failure secondary to short bowel syndrome. These patients have a high risk of acute rejection; for this reason bowel biopsies are performed as protocol and is the gold standard. Immunological follow-up of anti-HLA antibodies with Luminex® technology (LSA) was carried out in a patient with intestinal transplant and biopsies were performed to achieve an early diagnosis and a suitable histological correlation. Case report: A 20-year-old patient with short bowel syndrome secondary to extensive intestinal resection due to a complicated appendicitis underwent isolated bowel transplantation. The post-transplant immunological follow-up was performed with LSA and monthly intestinal biopsies. Antibodies with mean fluorescence intensity greater than 1500 were positive. During the pre-transplant protocol, the patient was screened for anti-HLA antibodies with negative results. Eleven months post-transplant, the screening test for anti-HLA Class I and II antibodies was positive; the specificity of the LSA test detected one specific donor antibody (DSA) and several antibodies against other molecular subtypes. The biopsy result was a mild acute cellular rejection and plasmapheresis therapy was started. The patient has not presented a clinical rejection, and at 21 months post-transplantation exhibits an adequate clinical and paraclinical evolution. Conclusions: This is the first small bowel transplant where immunological follow-up is done with LSA. We believe that the detection of DSA is a marker of acute humoral rejection that allows a diagnostic approach and a timely intervention

Intestinal and multivisceral transplantation / Transplante intestinal e multivisceral

Intestinal transplantation has shown exceptional growth over the past 10 years. At the end of the 1990’s, intestinal transplantation moved out of the experimental realm to become a routine practice in treating patients with severe complications related to total parenteral nutrition and intestinal failure. In the last years, several centers reported an increasing improvement in survival outcomes (about 80%), during the first 12 months after surgery, but long-term survival is still a challenge. Several advances led to clinical application of transplants. Immunosuppression involved in intestinal and multivisceral transplantation was the biggest gain for this procedure in the past decade due to tacrolimus, and new inducing drugs, mono- and polyclonal anti-lymphocyte antibodies. Despite the advancement of rigid immunosuppression protocols, rejection is still very frequent in the first 12 months, and can result in long-term graft loss. The future of intestinal transplantation and multivisceral transplantation appears promising. The major challenge is early recognition of acute rejection in order to prevent graft loss, opportunistic infections associated to complications, post-transplant lymphoproliferative disease and graft versus host disease; and consequently, improve results in the long run.

O transplante de intestino, ao redor do mundo, tem crescido de maneira sólida e consistente nos últimos 10 anos. No final da década de 1990, passou de um modelo experimental para uma prática clínica rotineira no tratamento dos pacientes com complicação severa da nutrição parenteral total com falência intestinal. Nos últimos anos, vários centros têm relatado uma crescente melhora nos resultados de sobrevida do transplante no primeiro ano (ao redor de 80%), porém, a longo prazo, ainda é desafiador. Diversos avanços permitiram sua aplicação clínica. O surgimento de novas drogas imunossupressoras, como o tacrolimus, além das drogas indutoras, os anticorpos antilinfocíticos mono e policlonal, nos últimos 10 anos, foi de suma importância para a melhora da sobrevida do transplante de intestino/multivisceral, mas, apesar dos protocolos bastante rígidos de imunossupressão, a rejeição é bastante frequente, podendo levar a altas taxas de perdas de enxerto a longo prazo. O futuro do transplante de intestino e multivisceral parece promissor. O grande desafio é reconhecer precocemente os casos de rejeição, prevenindo a perda do enxerto e melhorando os resultados a longo prazo, além das complicações causadas por infecções oportunistas, doenças linfoproliferativas pós-transplante e a doença do enxerto contra hospedeiro.

Microsurgical techniques for experimental kidney transplantation and general guidelines to establish studies about transplantation immunology

Experimental models of organ transplantation played a crucial role to establish the principles of transplantation immunology. The renal transplantation in rodents became the most used model to study the mechanisms of allograft rejection. To perform it, it is necessary to master the microsurgery techniques and the research group should cooperate with other specialists in the field. In this article we review the surgical techniques employed in rats, and we draw guidelines to establish studies about transplantation immunology.

Os princípios da imunologia do transplante estabeleceram-se após o surgimento de modelos experimentais. Esses modelos foram fundamentais para descoberta de mecanismos de tolerância imunológica e as bases genéticas da reação de rejeição. Transplante renal em roedores utilizando técnicas de microcirurgia tornou-se o modelo ideal, e abriu um novo horizonte para condução de pesquisas sobre imunologia e fisiologia de transplantes. Neste artigo revisamos as técnicas de transplante renal, e esboçamos diretrizes para elaboração de estudos imunológicos em modelos de rejeição.