Immune response capacity after human splenic autotransplantation: restoration of response to individual pneumococcal vaccine subtypes

OBJECTIVE: To evaluate features of general immune function, in particular the restoration of the humoral immune response to pneumococcal capsular polysaccharides, in humans undergoing a spleen autotransplantation after splenectomy because of trauma. SUMMARY BACKGROUND DATA: After splenectomy, patients have an increased risk of overwhelming infection or sepsis involving encapsulated bacteria such as pneumococci. The value of human spleen autotransplantation after splenectomy because of trauma has long been questioned. Mononuclear phagocyte system function appeared to be similar to that in splenectomized persons. The presence of specific antipneumococcal antibodies would allow other parts of the mononuclear phagocyte system, such as those in the liver, to phagocytose opsonized bacteria. METHODS: Ten consecutive patients undergoing splenectomy followed by autotransplantation were compared with the next 14 consecutive patients undergoing splenectomy alone. After a minimum of 6 months, the patients were vaccinated with 23-valent pneumococcal vaccine. Blood samples were taken at the time of vaccination and after 3 and 6 weeks for antipneumococcal capsular polysaccharides IgM and IgG enzyme-linked immunosorbent assay against types 3, 4, 6, 9, 14, and 23. Splenic regrowth was evaluated by scintigraphy. RESULTS: Surprisingly, several of the nonautotransplanted patients showed scintigraphic activity, indicating the presence of either accessory spleens or traumatic seeding (splenosis). Significant antibody titer increases (more than twofold) were found for both IgM and IgG in the autotransplanted patients. Splenectomized-only patients showed no significant increase in Ig levels in patients without splenic regrowth and partial improvement in patients with splenosis/accessory spleens. CONCLUSIONS: Considering this significant antipneumococcal antibody increase, spleen autotransplants can be expected to permit an adequate humoral response to pneumococcal infections and presumably also to other TI-2 antigens, and to protect against overwhelming postsplenectomy infection or sepsis.     

Phagocyte function after splenic autotransplantation

This study was designed to examine the role of splenectomy and autotransplantation with regard to the leukocyte/differential cell counts and the function of peripheral blood phagocytes. Eleven groups of 40 Wistar male rats in each group either underwent total splenectomies or sham operations. The splenectomized groups underwent autotransplantations with 10% through 90% of the weight of the intact spleen. The leukocyte count and the oxidative burst response of the blood leukocytes were measured in each group. It was shown that a total splenectomy did not alter the leukocyte/differential cell counts. Furthermore, the blood picture remained basically unchanged after an autotransplantation with 10% through 90% of the weight of the intact spleen. The phagocyte oxidative burst response was measured by chemiluminescence. The chemiluminescence response of these cells was reduced after a total splenectomy. The phagocyte oxidative burst response returned to normal levels following an autotransplantation. There was no correlation between the amount of autotransplanted spleen and the degree of the oxidative burst response. These findings indicated that a splenectomy results in a diminished phagocyte oxidative burst response and that a spleen autotransplantation returns this function to normal levels.     

Experimental study on function of regenerated splenic tissue after splenic autotransplantation

To prevent postsplenectomy overwhelming sepsis, splenic autotransplantation has been clinically attempted. However, function of regenerated splenic tissue after splenic autotransplantation has not been completely understood. Changes in weigh of regenerated splenic tissue, splenic blood flow, splenic immune responses and phagocytic function were studied for one year after splenic autotransplantation using Sprague-Dawley rats. At one year after autotransplantation, the weight of regenerated splenic tissue was increased to 80% of the originally implanted spleen and the blood flow was increased to 80% of the control spleen. The counts of lymphocytes and macrophages in the regenerated splenic tissue were significantly low at eight weeks after transplantation, however lymphocytes was increased to 58.8% and macrophages was increased to 29.5% of the control spleen at 16 weeks after transplantation. The blast formation of splenic lymphocytes was lower at the early stage after transplantation, thereafter, it was increased at the later time after transplantation. Microangiography of the regenerated spleen showed new capillaries around the implanted tissue 2 weeks after transplantation. These results suggested that the transplanted splenic tissue was regenerated to the similar structure to normal spleen and immunological function was recovered close to the normal splenic tissue.     

Laparoscopic splenic autotransplantation

Since 1990, we have performed splenic autotransplantation in more than 100 patients to treat splenic trauma, portal hypertension, myeloid metaplasia due to myelofibrosis, chronic lymphocytic leukemia, and Gaucher disease. The aim of this present study was to present splenic autotransplantation performed by laparoscopic means. A 33-year-old woman with severe splenic pain due to ischemia caused by multiple focal thromboses of splenic arterial branches was successfully treated by laparoscopic splenectomy and splenic tissue autotransplantation. The spleen was removed and cut in 20 fragments that were sutured to the greater omentum. This procedure was safely conducted with minor bleeding and no technical difficulties or complications. The postoperative follow-up of 12 months has been uneventful; the patient's pain disappeared on the first postoperative day. Hematologic, immunologic, tomographic, and scintigraphic examinations confirmed the functions of the splenic autotransplants. It is feasible and safe to perform splenic autotransplants by laparoscopic means.     

Splenic phagocytic function after partial splenectomy and splenic autotransplantation

We investigated splenic reticuloendothelial activity after splenic preservation procedures to determine their effect upon the phagocytic function of the spleen. We performed the following procedures in Sprague-Dawley rats: sham laparotomy, total splenectomy, hemisplenectomy, subtotal splenectomy, or total splenectomy with intraperitoneal splenic autotransplantation. At nine weeks after operation, phagocytic function of the spleen was determined by measuring radiocolloid uptake. Mean (+/- SEM) splenic phagocytic indices for sham laparotomy (41.2 +/- 2.9), hemisplenectomy (44 +/- 2.9), and subtotal splenectomy (43.2 +/- 5.2) were similar; however, the phagocytic index was reduced markedly after autotransplantation (15.8 +/- 2.2). These data demonstrate that the phagocytic function of the spleen after hemisplenectomy and subtotal splenectomy correlates highly with the weight of the splenic remnant; however, phagocytic function after autotransplantation remains reduced even after accounting for differences in splenic weight.     

自体脾腹膜后移植在创伤性脾破裂中的临床应用

目的探讨自体脾组织移植在治疗创伤性脾破裂的应用.方法对本组于2000年1月至2005年4月22例脾破裂行全脾切除后,再行自体脾组织腹膜后移植术.通过检测外周血IgM、IgA、IgG水平和B超,CT、99mTc扫描来观察移植脾片成活和吞噬功能恢复情况.结果术后随访均显示移植脾存活良好,脾功能满意.结论自体脾组织移植可作为严重脾外伤全脾切除术后保留脾功能的一个重要有效手段.     

脾损伤自体脾组织移植的临床应用

目的：探讨自体脾组织移植在临床中的应用。方法：总结32例脾外伤行全脾切除自体脾组织移植手术，其中采用大网膜囊内移植18例，去粘膜游离空肠段内移植12例，腹直肌鞘内移植2例。结果：术后随访均显示脾功能满意，尤以去粘膜游离空肠段内移植效果最好。结论：自体脾组织移植可作为严重脾外伤、全脾切除术后保留脾功能的一个重要有效手段，移植脾的功能恢复与血供有密切的关系。     

Regeneration and function of autotransplantation of splenic tissue after splenectomy

In traumatic rupture, it is often not possible to repair the spleen. Splenectomy results in increased susceptibility to sepsis with a high mortality rate. Autotransplantation of splenic tissue has been suggested, but its functional value is still in doubt, particularly the ability of autotransplanted spleen to resist intravenous bacterial challenge. The ability to sequestrate denatured^99mTc (technetium-99m) RBC (red blood cells) and to resist intravenous pneumococci was studied in sham-operated (control) rats, splenectomized rats, and splenectomized rats with autotransplanted spleen. Histopathologic tests were also performed. There was a gradual increase in the splenic sequestration of the denatured^99mTc RBC with a spleen-to-blood ratio of 0.19 to 1.5 at 2 and 30 weeks after the splenic reimplantation. Prior to 18 weeks after the splenic autotransplantation, no rat survived the intravenous pneumococcal challenge, but at 28–30 weeks, 80% of the rats survived the challenge indicating an increased splenic activity at this time. There was also a corresponding increase in splenic tissue weight from 241 mg at the time of autotransplantation to 417 mg beginning at the 24th week after the reimplantation. Four to 5 weeks after the transplantation, the spleens had a fairly normal histological architecture. The present study, therefore, indicates that autotransplanted splenic tissue is capable of restoring the ability to resist intravenously injected pneumococcal challenge, to sequestrate denatured^99mTc RBC, and to regenerate normal splenic tissue within 24–30 weeks after the reimplantation.

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Resumen En caso de ruptura traumática, con frecuencia no es posible reparar el bazo. La esplenectomá resulta en una susceptibilidad aumentada a la sepsis, con elevadas tasas de mortalidad. El autotransplante de tejido esplénico ha sido propuesto, pero su capacidad funcional se halla todavía en duda, particularmente en cuanto a su habilidad para resistir el desafío de una inyección bacteriana intravenosa. La habilidad para secuestrar corpúsculos rojos desnaturalizados y marcados con tecnecio-99m (Tc-99m CR) y de resistir neumococos intravenosos fue estudiada en operaciones fantasmas (Sham) en ratas controles, en ratas esplenectomizadas, y en ratas esplenectomizadas con bazos autotransplantados. Estudios histopatológicos también fueron realizados. Se observó un incremento gradual en el secuestro esplénico de los Tc-99m RC con una relación de bazo a sangre de 0.19 a 1.5 a las 2 y 30 semanas después de la reimplantación esplénica. Con anterioridad a las 18 semanas del autotransplante esplénico, ninguna rata sobrevivió a la inyección intravenosa de neumococos, pero a las 28–30 semanas, 80% de las ratas sobrevivieron este desafío, lo cual es indicativo de una actividad esplénica incrementada hacia esta época. También se produjo un aumento correspondiente del peso del tejido esplénico de 241 mg en el momento del autotransplante a 417 mg comenzando la 24^a semana después de la reimplantación. Cuatro a 5 semanas después del transplante, los bazos exhibían una arquitectura histológica bastante normal. En conclusión, el presente estudio indica que el tejido esplénico autotransplantado es capaz de restaurar la habilidad de resistir el desafío de una inyección intravenosa de neumococos, de secuestrar Tc-99m CR, y de regenerar tejido esplénico normal en el curso de 24–30 semanas después de la reimplantación.

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Résumé Lors des ruptures traumatiques, il est souvent impossible de suturer la rate. Les conséquences de la splénectomie sont représentées par une augmentation des infections avec un fort taux de mortalité. L'autotransplantation du tissu splénique a été proposé mais sa valeur fonctionnelle est toujours mise en doute en particulier en ce qui concerne l'aptitude de la rate autotransplantée à résister à la sépticémie. Les auteurs étudient l'aptitude à sequestrer les hématies dénaturées marquées aux^99mTc (technetium-99m) globules rouges (RBC) et la résistance contre le pneumocoque par voie intraveineuse chez des rats témoins opérés sans splénectomie, des rats splénectomisés et des rats splénectomisés avec autotransplantation splénique. Des examens histopathologiques sont aussi pratiqués. Il existe une augmentation graduelle dans la séquestration splénique des hématies marquées avec un rapport rate-sang de 0.19 à 1.5 à la deuxième et la trentième semaine après la réimplantation splénique. Aucun rat n'a survécu à l'injection de pneumocoque avant les 18 semaines et après autotransplantation, alors que à partir de la 28-ième à la trentième semaine, 80% des rats ont survécu à l'infection indiquant une augmentation de l'activité splénique à cette période. De même il a été observé une augmentation du poids tissulaire splénique concomittante de 241 mg au moment de l'autotransplantation, à 417 mg à partir de la 24 ème semaine après réimplantation. Quatre à 5 semaines après la transplantation, la rate a pratiquement récupéré une architecture histologique normale. Cette étude indique que le tissu splénique autotransplanté est capable de récupérer sa capacité de résistance contre l'infection par le pneumocoque injecté par voie intraveineuse, de séquestration des hématies dénaturées marquées au^99mTc et enfin de régénération du tissu splénique normal 24 à 30 semaines après la réimplantation.

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Presented at the Société Internationale de Chirurgie in Paris, September 1985.     

自体脾移植临床研究

目的探讨自体脾组织移植在严重脾损伤患者的应用及临床意义。方法46例严重脾损伤患者行脾切除术,其中26例行自体脾移植为治疗组,20例为对照组。观察血清免疫球蛋白的含量、NK细胞活性和T淋巴细胞转换率的变化。结果血清免疫球蛋白的含量两组lgG、lgA和脾移植lgM术前与术后相比较无显著差异(P>0.05)。两组NK细胞活性和T淋巴细胞转化率比较有明显差异(P<0.01)。结论自体脾移植术后患者机体免疫功能能维持在正常水平,是保留脾脏功能的有效措施之一。     

Reimmunization and splenic autotransplantation: A long-term study of immunologic response and survival following pneumococcal challenge

Splenic autografts have phagocytic function and increase survival after experimental sepsis. The long-term effect of transplant viability, phagocytic capacity, and immunologic responsiveness were evaluated. Rats were divided into experimental groups: control, splenectomized, and splenic autotransplant rats. Approximately one-half of the rats were immunized against pneumococcus. Twelve months later, the rats were reimmunized, and the pneumococcal antibody titers were measured. The effect of operation and immunization was determined by challenging rats with intravenously administered pneumococci. Bacterial clearance from the bloodstream was measured and mortality recorded. Spleens were weighed and examined histologically. In unimmunized rats, pneumococcus was cleared from the bloodstream of control rats, whereas splenectomized and splenic autotransplant rats demonstrated a progressive increase of pneumococci in the bloodstream. However, splenic autotransplant rats grew fewer bacteria after challenge (P < 0.05). All control rats survived. Thirty-three percent of splenic autotransplant rats were alive, but significantly fewer splenectomized rats (6%) survived (P < 0.05). After reimmunization, highest antibody titers were noted in control rats (P < 0.05). Splenic autotransplant rats had higher antibody titers than did splenectomized rats (P < 0.05). Reimmunized splenic autotransplant rats had greater survivorship (71%) when compared with reimmunized splenectomized rats (26%) (P < 0.003). At 1 year, transplants were smaller than control spleens (P < 0.001), although histologic integrity was maintained. Splenic autotransplantation results in better phagocytic function, improved response to reimmunization, and increased survival after pneumococcal challenge and may be an important measure in preventing postsplenectomy sepsis.     

Reticuloendothelial clearance and splenic mononuclear cell populations after resection and autotransplantation

Although the preservation of splenic tissue may prevent overwhelming infection after splenectomy, the degree of protection conferred by small remnants has not been optimal. We investigated whether either splenic reticuloendothelial clearance of a blood flow-dependent colloid or macrophage and T-cell populations might be altered by resection or autotransplantation of the spleen. Our results have shown that bloodstream reticuloendothelial clearance of technetium 99m sulfur colloid is not impaired by splenectomy, partial resection of the spleen, or splenic autotransplantation. Such clearance is dependent on spleen weight and is not related to differences in either macrophage or helper or suppressor T-cell populations. This suggests that autotransplantation of the spleen is inferior to preservation of even a small hilar remnant and implies that repair or partial resection of the spleen will provide greater protection than autotransplantation.     

Heterotopic splenic autotransplantation: a therapeutic option in splenic trauma]

The Authors report two cases of splenectomy for trauma, followed by heterotopic autotransplantation of splenic tissue in omental pockets. A follow-up nuclear scan and ultrasonography showed function and growth of the splenic implants. The pertinent surgical literature is reviewed.     

Experimental studies on splenic autotransplantation in rats

To determine if splenic implants in the body regain vascularization and grow, and to determine the effects of any interaction between implant and remnant on growth of these spleen fragments, we conducted experiments on rats. 1) Spleen fragments were implanted in the omentum (20 cases), in the subcutaneous space (20 cases), or in the liver (10 cases), and the weight of splenic portions and its histological findings were observed 12 and 24 weeks after operation. The best splenic growth was observed in the group of implant in the omentum. 2) Total, 4/5, 2/3, 1/3 and 1/5 spleen were implanted in the omentum and the weight of implants were measured 6 weeks after the operation. The rate of growth of implanted spleen was the highest in the group of 1/5 and was the lowest in the group of whole spleen. 3) Two groups of rats underwent 1/3 splenectomy, and the 1/3 spleen portions was implanted in the omentum. One group had the remaining 2/3 spleen removed, the other group had the remaining 2/3 spleen left in place. In group at 6, 12 and 24 weeks postoperatively the splenic portions was weighed. The implants regenerate with time in rats of both groups. The rate of weight-gain was, however, slow in the group with 2/3 spleen and there was no regeneration on the remaining 2/3 spleen.     

Evaluation of antibody response to the heptavalent pneumococcal conjugate vaccine in pediatric chronic kidney disease

Pneumococcal vaccination has been recommended for immunocompromised children, including patients with chronic kidney disease. We determined pneumococcal immunoglobulin (Ig)G antibodies to serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F before and after 48 pediatric patients with chronic renal failure were administered heptavalent conjugated pneumococcal vaccine. The patients were between 1 and 9 years of age and were separated into a conservative treatment group (Group 1) and a dialysis group (Group 2). The antibody response to the vaccinal serotypes was evaluated by measuring antibody concentrations before the first dose and 60 days after the second one. Pre-vaccinal IgG concentrations ≥0.35 μg/ml were detected for all serotypes in at least 50% of the patients in both groups. Patients from both groups showed a statistically indistinguishable behavior in terms of the medians of post-vaccination IgG levels. An “adequate” vaccine response was defined as a post-immunization level of specific pneumococcal serotype antibody ≥0.35 μg/ml, based on the World Health Organization’s (WHO) protective antibody concentration definition for pneumococcal conjugate vaccines, or on a fourfold increase over baseline for at least five of the seven antigens of the vaccine. An “adequate” vaccinal response was obtained in 100% of the patients of both groups using WHO’s definition, or in 45.8% of Group 1 patients and 37.5% of Group 2 patients when the criterion was a fourfold antibody increase over baseline antibody concentrations.     

Feasibility of correction of insulin insufficiency after autotransplantation of splenic tissue in duodenopancreatectomy

Autotransplantation of splenic tissue in two patients after total duodenopancreatectomy and splenectomy for trauma of the duodenum and pancreas has demonstrated positive results and stable compensation of insulin insufficiency in two cases. Experimental studies of autotransplantation of splenic tissue carried out on 20 cats and 100 rats with pancreatectomy- and alloxan-induced diabetes demonstrated good results too. This method may be regarded as the variant of repair therapy with stromal stem-cells of the spleen.     

Influenza vaccine antibody responses in lung transplant recipients

CONTEXT: Lung transplant recipients are at high risk of morbidity and mortality from influenza infection because of altered lung physiology and immunosuppression. Annual influenza immunization is recommended, but the ability to mount an antibody response may be limited by immunosuppressant medications. OBJECTIVE: To compare the antibody response rate to influenza vaccine in lung transplant recipients to healthy controls. DESIGN: Open label study. SETTING: Lung transplant clinic and General Clinical Research Center at a university hospital. SUBJECTS: Sixty-eight single and bilateral lung transplant recipients and 35 healthy controls were enrolled in October and November 2002. METHODS: Each individual underwent blood sampling before receiving the 2002-2003 influenza vaccine and 4 weeks later. Influenza antibody concentrations were measured by hemagglutination inhibition assay. Vaccine response rates (antibody concentration >40 hemagglutination units and at least 4-fold increase in antibody concentration) were compared using chi2. The influence of specific immunosuppressants on vaccine response was compared. RESULTS: The influenza vaccine response rate for lung transplant recipients was 29/68 (43%) and 22/35 (63%) for the healthy individuals (P < .05; chi2). Among the recipients, mycophenolate mofetil was associated with poorer influenza vaccine antibody response (> 40 hemagglutination units) (62% vs 91%; P = .01), whereas sirolimus (91% vs 63%; P = .02) was associated with better influenza antibody response compared to those not taking mycophenolate mofetil or sirolimus, respectively. CONCLUSION: Lung transplant recipients had lower influenza vaccine response rates than healthy individuals. Influenza vaccine antibody response is influenced by concomitant administration of mycophenolate mofetil or sirolimus. Future studies should measure protection from influenza infection conferred by immunization and alternative vaccination strategies.