Ligament reconstruction in thumb carpometacarpal joint instability: A systematic review.

In thumb carpometacarpal (CMC) instability, laxity of the ligaments surrounding the joint leads to pain and weakness in grip and pinch strength, which predisposes the patient to developing CMC joint arthritis. Recent advancements in joint anatomy and kinematics have led to the development of various surgical reconstructive procedures. This systematic review outlines the available ligament reconstruction techniques and their efficacy in treating nontraumatic and nonarthritic CMC instability. Additionally, we aimed to provide evidence which specific ligament reconstruction technique demonstrates the best results. Four databases (Embase, MEDLINE, Web of Science, and Cochrane Central) were searched for studies that reported on surgical techniques and their clinical outcomes in patients with nontraumatic and nonarthritic CMC instability. Twelve studies were analyzed for qualitative review, including nine different surgical ligament reconstruction techniques involving two hundred and thirty thumbs. All but one of the reported techniques improved postoperative pain scores and showed substantial improvement in pinch and grip strength. Complication rates varied between 0% and 25%. The included studies showed that ligament reconstruction effectively alleviated the patients' complaints regarding pain and instability, resulting in overall high patient satisfaction. Nevertheless, drawing definitive conclusions regarding the superiority of any ligament reconstruction technique remains challenging owing to the limited availability of homogeneous data in the current literature.

Immunological response of sheep to injections of plasmids encoding Toxoplasma gondii SAG1 and ROP1 genes.

Infection with the intracellular protozoan parasite Toxoplasma gondii (T. gondii) causes health problems to both humans and livestock and has a large economic impact worldwide. The immune response in sheep following infection with T. gondii was evaluated using six different combinations of plasmid DNA, recombinant antigen and adjuvant. Sheep were generally vaccinated twice by intramuscular injection with plasmid DNA containing gene sequences for either the surface antigen (SAG1) or the rhoptry protein (ROP1) of T. gondii. Two of the groups injected with plasmid DNA SAG1 were boosted with recombinant protein (SAG1). We investigated the efficacy of including oligodeoxynucleotides (ODN) that contain CG motifs (CpG) and the gene coding for ovine granulocyte-macrophage colony stimulating factor (GM-CSF) as potential adjuvants. Administration of the plasmid encoding the ROP1 gene significantly enhanced both IFN-gamma production from peripheral blood cells when cultured in vitro with Toxoplasma antigen, and ROP1-specific IgG1 and IgG2 antibody levels present in serum. However, injection with SAG1 did not stimulate IFN-gamma production. These results indicate the potential of ROP1, given as plasmid DNA, as a potential vaccine candidate to protect sheep against T. gondii infection.

An 11-Year Overview of the Belgian Donor and Transplant Statistics Based on a Consecutive Yearly Data Follow-up and Comparing Two Periods: 1997 to 2005 Versus 2006 to 2007.

BACKGROUND: The Belgian Transplant Coordinators Section is responsible for the yearly data follow-up concerning donor and transplantation statistics in Belgium and presents herein a 10-year overview. METHODS: The procurement and transplant statistics were compared between 2 periods: Period 1 (P1, 1997-2005) versus Period 2 (P2, 2006-2007). RESULTS: The kidney and liver waiting lists (P1 vs P2) showed an overall decrease for a period of 2 consecutive years in P2; kidney (-170 patients; -18%), and liver (-83 patients; -34%). All other waiting lists (heart, lung, pancreas) remained stable. Mean ED further increased (P1 vs P2); 229 (P1) versus 280 (P2, +22.27%). Non-heart-beating donors were significantly (+288%) more often procured in P2. Mean donor age was 37.9 +/- 17.8 years (P1) versus 46.5 +/- 19.9 years (P2), and mean organ yield per donor was 3.48 +/- 1.7 (P1) versus 3.38 +/- 1.8 (P2). Overall transplant activity per million inhabitants increased 21.1%. CONCLUSION: For 2 consecutive years, the Belgian statistics showed significantly increased donor activity with an impact on waiting list dynamics and transplantation. The mean organ yield per donor was not influenced despite an increased average age and change in reason for death.

Change in donor profile influenced the percentage of organs transplanted from multiple organ donors.

We hypothesized that the change in donor profile over the years influenced the percentage of transplantations. We reviewed medical records for all multiple-organ donors (MODs) within our network. The percentage of transplanted organs was compared between 1991-1992 (A) and 2006-2007 (B). In period A, 156 potential MODs were identified compared with 278 in period B. Fifteen potential donors (10%) in period A and 114 (41%) in period B were rejected because they were medically not suitable (40% vs 75%) or there was no family consent (60% vs 25%). Of the remaining effective MODs (141 in period A and 164 in period B), mean (standard deviation = SD) age was 34 (5) years vs 49 (17) years (P < .001). Brain death resulted from craniocerebral trauma in 69% vs 39%, cerebrovascular disease in 24% vs 46%, hypoxia in 4% vs 15%, and brain tumor in 2% vs 0.6% (P < .001). Chest trauma was present in 19% vs 9% (P < .01). The percentage of MODs who received mechanical ventilation for more than 5 days was 8% vs 24% (P < .001). The percentage of organs transplanted in periods A vs B was kidneys, 97% vs 79%; livers, 64% vs 85%; hearts, 60% vs 26%; lungs, 7% vs 35%; and pancreas, 6% vs 13% (P < .001). The number of referred potential MODs increased by 80%, resulting in a small increase in effective MOD organs (17%), mainly because of medical contraindications. The MOD profile changed to older age, fewer traumatic brain deaths, and longer ventilation time. We transplanted more livers, lungs, and pancreases but fewer kidneys and hearts.

Importance of informatics and database management in transplant coordination.

Advanced use of informatics within modern health care has become essential. Transplantation and transplant coordination, a high technically advanced and very specific niche within health care, is strongly depending on time management and exclusion of possible pitfalls within an acute organization at both the donor and the recipient sites. Based on the increased donor and transplant activity, we stratified two goals. The first goal was to improve working methods at the donor site. The second goal was to reduce administrative tasks and increase quality follow-up at the recipient side. For the donor process, we designed a Donor Database, that was created for donor registration and quality data reporting. A 24/24 h accessible website was created and was linked with clinical pathways and reports. For the liver transplant process, we built another database system in FileMaker pro, creating a quality follow-up and reporting methods. Based on a retrospective analysis and review of two executive time periods, we saw a clear improvement in the donor reporting method, and the quality of the procedure. Possible mistakes within the acute organization were easily detected based on clinical pathways provided by the website on one hand, and integrated within the database system on the other hand. We succeeded in bringing high-quality informatics to the floor of donor and transplant procedures and follow-up. Retrospective analysis showed a definite improvement, with a positive impact on data reporting, time management and administrative follow-up.

Living donor kidney transplantation: analysis of the first 40 cases performed in UZ Leuven.

Living donation kidney transplantation has been popular worldwide to try to increase the donor pool. In Belgium, the rate of living donation kidney transplantation has been traditionally relatively low compared to other countries. This is--in part--due to the relatively higher cadaveric organ offer that is available in Belgium (around 25 donors per million inhabitants), compared to other countries. However, the increasing waiting times on cadaveric waiting list and the superiority of the results of live donation versus cadaveric kidney transplantation have led to a reappraisal of this strategy. In our center a living donation kidney transplant programme was started in 1997. Since then 40 cases of live donation kidney transplantation have been performed and are reported herein.

Abdominal Transplant Surgery and Transplant Coordination University Hospitals Leuven 1997-2007: an overview.

The transplant surgery and transplant coordination department was created in 1997 to meet up with the demand of the growing abdominal transplant surgery and organ procurement activity at the University Hospitals in Leuven. Since then, the procurement activity has increased and is currently distributed within the University Hospital Gasthuisberg and a network of approximately 25 collaborative hospitals. The profile of the donors has changed with older donors and more co-morbidity factors (obesity, hypertension, etc.). This donor activity represents approximately 30% of the national donor pool. Over the last 10 years, more than 1100 kidneys, more than 500 livers, approximately 50 pancreas, and 5 intestines have been transplanted in both adults and children. One year survival equal to- or exceeding 90% has been achieved for all abdominal organs and this compares favorably with international registries. More than 40 multi-visceral transplants {liver in combination with abdominal (kidney, pancreas, intestine) or thoracic (heart, double lung, heart-lung) organs} have been performed with results equivalent to isolated liver transplants and very little immunological graft loss (probably due to the immunoprotective effect of the liver). A live donation program was started for the kidney (40 cases) and for the liver (10 cases) in adults and children and no surgical graft loss has been seen so far. Introduction of new machine perfusion systems (and development of donor protocols) has made it possible to restart a non-heart-beating donor program for kidney transplantation. Experimental demonstration that livers tolerate short periods of warm ischemia has also allowed to start liver transplantation from non-heart-beating donors. In the future, machine perfusion of livers, viability testing, and biological modulation are likely to widen the use of marginal livers for transplantation and improve the results. An immunomodulatory protocol proven in the lab to induce the development of regulatory T cells has been applied clinically to 5 consecutive intestinal transplants. All 5--at the time of writing--have been rejection-free and have achieved nutritional independence. Continuous research and development is warranted to increase the organ donor pool (currently the solely limiting factor of transplantation) and to optimize long-term graft and patient outcome.

Evolution in allocation rules for renal, hepatic, pancreatic and intestinal grafts.

Organ transplantation is the victim of his own success. The results of transplantation are excellent and more patients are activated on the waiting list. The need for organs exceeds the supply. Which criteria are used to allocate available grafts to patients on the waiting list ? Organ allocation and finding the "best match" between donor and recipients, is the goal of Eurotransplant, the organ sharing organization for seven European countries (Austria, Croatia, Germany, Luxemburg, Slovenia, The Netherlands and Belgium). Last decade, the allocation system has switched from a "center-driven" (organ allocated to a center) to a "patient-driven" system (organ allocated to a particular patient). For the allocation of abdominal organs some general allocation rules are followed: blood group compatibility, priority for high urgencies. The allocation of kidneys is based on a point score system based on waiting time, HLA and donor location (to reduce the cold ischemia time). In addition to this standard allocation procedure, there are still specific procedures for pediatric recipients and for candidates > or = 65 year old. There is also an "acceptable" mismatch program for recipients at high immunological risk. The liver allocation system recently changed and is now based on the MELD score, a formula that calculates the probability of death within 3 months on the waiting list. For pancreas and intestine, the system is based on blood group, medical urgency, waiting time, donor region and weight (for intestine).

Donor categories: heart-beating, non-heart-beating and living donors; evolution within the last 10 years in UZ Leuven and Collaborative Donor Hospitals.

Over the past 10 years, the University Hospitals Leuven and their group of Collaborative Donor Hospitals (approximately 20) have tried to maximize their contribution to the national and Eurotransplant donor pool. In this time period, 1042 potential donors and 703 effective donors were coordinated and their organs allocated through Eurotransplant. This activity represented approximately 30% of the national donor pool and approximately 32% of the national organ pool. For Belgium, the non-heart-beating donor activity represented 11.38% of all donors in 2006. Since 1997, 167 potential live donors have been screened in our center. Of these, 48 transplants (28.74%) (39 kidneys--9 livers) have been performed. A boost of screened candidates was seen over the last 3 years, with a 500% increase of records being evaluated. Although the Belgian live donation activity remains one of the lowest in the world, there has been a clear increase over the last 3 years with about 10% of all kidney transplant activity originating now from live donors.

Overview of the Belgian donor and transplant statistics 2006: results of consecutive yearly data follow-up by the Belgian Section of Transplant Coordinators.

BACKGROUND: The Belgian Section of Transplant Coordinators, created in 1997 under the auspices of the Belgian Transplant Society, is in charge of the collection of the national data about donor/procurement activities. METHODS: Data are collected in all Belgian transplant centers. An annual report is finalized by combining these data with data from the Eurotransplant database. RESULTS: An increase of both potential donors (n = 501, +14.4%) and effective donors (n = 273, +16.7%) was observed in 2006 versus 2005. Among effective donors, 28 were non-heart-beating donors (10.25%). Overall donor ratio was 26.26 donors per million inhabitants. Within potential donors, absence of organ harvesting was due to medical contraindications (28%), family refusal (13%), or legal refusal (2%). Donor mean age was 46.4 years and mean organs/donor was 3.21 +/- 1.7. An overall reduction of Belgian waiting lists was observed in 2006 as compared with 2005 (-5.7% for kidney, -25.7% for liver, -9.4% for heart, -6.7% for lung, and -11.7% for pancreas), while waiting list mortality was 18% for liver, 11% for heart, and 7% for lung. As compared with 2005, transplant activities increased for kidney (n = 485, +24.3%), heart +/- lungs (n = 73, +7.3%), and lungs (n = 83, +39.4%) but decreased for liver (n = 236, -2.1%). Living donation represented 8.45% for kidney (+28.1% vs 2005) and 8% for liver transplantation (-29.6%). CONCLUSION: Globally, a marked increase of procurement and transplant activities was observed in 2006, allowing to limit waiting list and waiting list mortality. Further increase of living donor activity and non-heart-beating donation remains necessary to extend the donor pool.

Liver transplantation using non-heart-beating donors: Belgian experience.

UNLABELLED: Mortality on liver transplantation (OLT) waiting lists has increased dramatically. Until recently, non-heart-beating donors (NHBD) were not considered suitable for OLT, because of a higher risk of primary graft nonfunction (PNF) and biliary strictures. However, recent experimental/clinical evidence has indicated that NHBD-OLT is feasible when the period of warm ischemia is short. PURPOSE: To characterize the results of NHBD-OLT in Belgium, a survey was sent to all Belgian OLT centers. RESULTS: Between January 2003 and November 2005, 16 livers originating from NHBD were procured and transplanted. The mean donor age was 48.8 years, including 9 males and 7 females with mean time of stop-therapy to cardiac arrest being 18 minutes and from cardiac arrest to liver cold perfusion, 10.5 minutes. Mean recipient age was 52.2 years including 12 males and 4 females. Mean cold ischemia time was 7 hours 15 minutes. No PNF requiring re-OLT was observed. Mean post-OLT peak transaminase was 2209 IU/L, which was higher among imported versus locally procured grafts. Biliary complications occurred in 6 patients requiring re-OLT (n = 2), endoscopic treatment (n = 2), surgical treatment (n = 1), or left untreated (n = 1). These tended to be more frequent after prolonged warm ischemia. Graft and patient survivals were 62.5% and 81.3%, respectively, with a follow-up of 3 to 36 months. CONCLUSION: This survey showed acceptable graft/patient survivals after NHBD-LT. The NHBD-liver grafts suffered a high rate of ischemic injury and biliary complications and therefore should be used carefully, namely with no additional donor risk factors, lower risk recipients, and short cold/warm ischemia.

Liver transplantation using livers from septuagenarian and octogenarian donors: an underused strategy to reduce mortality on the waiting list.

Shortage of liver grafts is the only limiting factor for application of liver transplantation and causes an increasing mortality on the waiting list. Very old donors (>70 to 80 years old) are rarely referred to transplant centers because of the assumption that these livers will not work properly. Alternatively, transplant teams may be reluctant to use these very old livers due to the risk of poor posttransplant outcome. We reviewed our experience with seven liver transplantations using very old donor livers. We found that the results in terms of graft function and patient survival are adequate. Interestingly, the majority of these donors originated from a single referring donor unit (of more than 20 units who belong to our donor network) that systematically refers all brain-dead donors to the transplant center, independent of the age of the potential donor. This implies that many of these donors are left undetected in other units. In conclusion, very old donors should be referred to transplant centers since results of transplantation with these grafts are favorable.

Type of donor aortic preservation solution and not cold ischemia time is a major determinant of biliary strictures after liver transplantation.

The development of biliary strictures (BSs) after liver transplantation (LT) continues to affect 10% to 30% of patients, causing substantial morbidity. The cause of BSs is multifactorial, including technical, immune, and, in particular, ischemic factors. The importance of adequate flushing of the peribiliary arterial tree has been stressed. We hypothesized that high-viscosity (HV) preservation solutions in the donor do not completely flush the small donor peribiliary plexus, leading to inadequate preservation of the bile ducts and posttransplant BSs. To test this hypothesis, we retrospectively compared the incidence of BSs in 2 groups of adults undergoing LT using different types of aortic preservation solution in the donor: group 1 (n = 24), low-viscosity (LV) Marshall solution; and group 2 (n = 27), HV University of Wisconsin (UW) solution. All donors in both groups received additional portal flushes with UW. All LTs were performed between November 1995 and August 1998 at 2 centers by the same surgeon, eliminating a technical bias. Terminal duct-to-duct anastomosis was performed in all recipients except 1 patient in group 1, who underwent a bile duct-to-jejunum anastomosis. BSs were first suspected on clinical and biochemical grounds and then confirmed by endoscopic retrograde cholangiopancreatography. Identical medical protocols were used in all patients. One-year patient survival rates in groups 1 and 2 were 92% and 100%, respectively (P =.9). One-year graft survival was identical to patient survival. The incidence of BSs in group 1 was 4.1% (1 of 24 patients), compared to 29.7% in group 2 (8 of 27 patients; P =.02). The BS in group 1 occurred 4 months post-LT and was anastomotic. BSs in group 2 occurred between 1 and 12 months post-LT and were anastomotic, extrahepatic, intrahepatic, or combined intrahepatic and extrahepatic. There were no significant differences in the following factors between groups 1 and 2: donor age, local versus imported liver, split-liver or full-liver transplantation, incidence of multiple vessels in the donor liver, indications for LT, recipient age, T-tube versus no T-tube, post-LT peak aspartate aminotransferase level, and treatment for rejection. There was no hepatic artery thrombosis or primary nonfunction in either group. Interestingly, cold ischemia time (CIT) was longer in group 1, which had the least incidence of BSs (692 +/- 190 v 535 +/- 129 minutes in group 2; P =.001). Follow-up was longer in group 1 (28.9 +/- 8.3 v 15.6 +/- 8 months in group 2; P =.0001). Preservation costs per procurement were 1.9 times greater in the UW group than in the Marshall group. Donor aortic flushing with an HV preservation solution leads to more frequent BSs compared with an LV preservation solution. The impact of preservation solution outweighs the previously described deleterious impact of prolonged CIT. Mixed preservation solution (Marshall solution in the aorta, UW solution in the portal vein) might protect against BS formation while providing optimal liver graft preservation, function, and survival despite a mean CIT longer than 10 hours.

Soluble HLA in human body fluids.

There is a growing body of information about the soluble forms of HLA in serum but there are only a few reports discussing sHLA in other body fluids. We quantitated sHLA-I and sHLA-II concentrations in sweat, saliva and tear samples from five normal individuals with known HLA-phenotypes. We also studied sweat samples from an additional 12 normal nonphenotyped subjects, as well as in CSF of 20 subjects with different illnesses, using solid phase enzyme linked immunoassay. Sweat, saliva and tears from normal subjects were found to contain very low or nondetectable amounts of sHLA-I. In contrast, sHLA-II molecules were found in each of these body fluids, although, with considerable variation between individuals. The presence of sHLA-II in saliva was further confirmed by Western-blotting. It was observed that sHLA-II having molecular mass of 43,900 and 18,100 daltons was comparable with that found in serum from normal individuals. In addition, no association of sHLA-II levels with allospecificities in either body fluid or in serum was apparent. The results of CSF sHLA concentrations in different diseases were as follows: (1) High CSF SHLA-I levels were measured during viral encephylitis (n = 3), while none of these patients contained sHLA-II in CSF; (2) The levels of sHLA-II, but not sHLA-I were elevated in CSF of patients during seizure (n = 6) and of patients with neonatal hepatitis (1 of 2) or with connective tissue disease accompanied with viral infection (n = 2); (3) No CSF sHLA-I or sHLA-II could be detected at polyneuropathy (n = 2), or in patients with syphilis (n = 3), or leukemia (n = 2) with evidence of neurologic involvement of central nervous system. Taken together, it may be concluded that the presence of sHLA in several body fluids is physiologically normal. It appears that sHLA-II is the predominant class of HLA molecules present in different body fluids. We propose that the system responsible for sHLA-II production in various body fluids must involve different mechanisms than those responsible for sHLA-I synthesis in serum.

Soluble HLA-I in rheumatic diseases.

OBJECTIVE: To study serum levels of Class I soluble HLA (sHLA-I) in patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), polymyositis or dermatomyositis (PM/DM) or scleroderma and to assess the possible influence of ethnic factors on concentration in each disease group. METHODS: Solid-phase enzyme linked immunoassay was used to measure sHLA-I in the serum of 385 patients with varied ethnic backgrounds (American-Caucasians, African-Americans, Georgian-Caucasians) with rheumatic diseases. Studies on patients were compared to similar measurements of 189 healthy individuals. RESULTS: Mean sHLA-I levels were significantly higher in patients with SLE than those observed in healthy individuals or other rheumatic diseases. Highest concentrations were present in Georgian-Caucasian patients with SLE. American-Caucasian patients with RA or scleroderma had higher sHLA-I levels than normal Caucasian individuals. The majority of patients with PM/DM in all ethnic subgroups were low secretors of sHLA-I. CONCLUSION: Mechanisms underlying the secretion of sHLA-I appear to differ among the rheumatic diseases studied and various ethnic groups. These genetic differences in sHLA-I secretion could be associated with ethnic and pathophysiologic differences among these rheumatic diseases.

Tumor-associated antigens are cytokine inducers and hyporeactivity factors to the immune system.

We investigated possible mechanisms leading to the inhibition of the immune system in people with chronic disorders. Tumor cell produce protein released into the circulation, such as tumor associated antigens, may play an important role in processes preceding paralysis of the immune system. To test this hypothesis the following tumor associated antigens were used: AFP, OFP, CA-125, CA-50 and CA-19-9. Their role was assessed by modulating cytokine production in cord blood lymphocytes and peripheral white blood cells obtained from grown population of patients treated with colostrinin, an cytokine inducer. PHA, LPS and colostrinin were used as positive control in those essays. Each antigen tested individually induced IFN, TNF alpha and IL-6 in dose dependent fashion. None of the tested cytokines were spontaneously released by the cells. Data generated from these experiments indicated that tumor associated antigens are inducing type 1 cytokines in similar fashion as LPS or colostrinin. However, lymphocytes taken from patients undergoing therapy with colostrinin revealed progressive loss capability to produce type 1 cytokines as they did in case of colostrinin. The loss of the capability to respond to antigen may represent phenomenon leading to immune tolerance.

Serologic allogeneic chimerism.

BACKGROUND: At least some transplanted livers secrete soluble human leukocyte antigens (sHLA) of donor phenotype into the body fluids of recipients. The individuals in whom this phenomenon occurs are by definition serologic allogeneic chimeras. Because an allogeneic transplanted liver may induce tolerance to itself and other organs in animals of the donor strain, and because maintenance of a soluble antigen in the circulation of any animal in sufficient quantity for a sufficient period generally leads to tolerance, this phenomenon may be biologically important. This study was performed to determine how common this phenomenon is and whether it occurs after transplantation of organs other than the liver. METHODS: We studied 445 serum samples obtained from transplant recipients (liver, n=12; kidney, n=18; and heart, n=8) before and at various intervals after transplantation. All patients studied had allografts that had functioned for more than 1 year. We used an enzyme-linked immunosorbent assay to quantitate sHLA-A2 and sHLA-A1/A3/A11 (as a cross-reacting group). Donor and recipient combinations were selected in which measurable allotypes in donors were not present in recipients. In some instances, an additional allotype was present in a recipient but not in a donor. RESULTS: All liver transplant recipients had detectable donor sHLA in their serum samples after transplantation. In 72% of kidney and 50% of heart transplant recipients, donor sHLA was found persistently in serum samples obtained after transplantation. Interestingly, all heart transplant recipients of HLA-A3, but none of HLA-A2, had detectable donor sHLA in their serum samples, a finding that may be due to technical reasons. High and stable serum concentrations of donor sHLA characterize long-term stable allograft function. CONCLUSIONS: Donor sHLA is produced by all transplanted livers, most transplanted kidneys, and at least half of (but probably more) transplanted hearts. The hypothesis that donor sHLA may be tolerogenic to liver transplants can be expanded to include kidney and heart transplants.

Soluble HLA class I antigens in patients with type I diabetes and their family members.

Our objective was to study a possible contribution of MHC genes to S-HLA-I secretion in patients with Type I diabetes. Quantitatively, we used a highly sensitive enzyme-linked immunoassay to measure S-HLA-I in the serum of a total of 39 patients with Type I diabetes, as well as 36 kinships of 12 diabetic patients and 82 normal individuals with known HLA-phenotypes. S-HLA-I levels were abnormally elevated in patients or their non-diabetic relatives compared to normal controls (p < 0.0009). No complete HLA-haplotype had been identified to be correlated with high or low S-HLA-I secretion. Only the HLA-A23 or A24 (splits of HLA-A9) positive individuals sera were found to contain high S-HLA-I concentrations in all populations studied. The difference in S-HLA-I levels of HLA-A24 patients (n = 4) or their HLA-A24 positive non-diabetic relatives (n = 10) to the group of HLA-A24 normal controls (n = 15) was statistically highly significant (p < 0.0005 and p < 0.0009, respectively). The results suggests that HLA-A24 may confer additional independent risk for the disease expression in male children but not in female siblings. Nevertheless, the data implies that the patients or their non-diabetic relatives carrying the HLA-A24 have increased risk of developing ICA associated with high S-HLA-I levels compared to HLA-A24 negative probands or their kinships with low levels of S-HLA-I. This effect occurred irrespective to other diabetes related HLA-DR alleles. In summary, the results show a pronounced genetic heterogeneity of Type I diabetes with MHC control of the expression of S-HLA-I and possible involvement of hormonal factors that might potentiate a specific synthesis of S-HLA-I. The findings have implications for identifying individuals with a possible risk for developing the disease.

Soluble fraction of class I human histocompatibility leukocyte antigens in the serum of liver transplant recipients.

In previous studies we reported a solid-phase, enzyme-linked immunoassay (ELISA) that can be used to quantitate the soluble fraction of human histocompatibility leukocyte class I antigens (S-HLA-I) and study their relevance in transplantation. In this study we determined the concentration and distribution of S-HLA-I in patients with end-stage liver disease (ESLD), as well as in liver transplant recipients. Sera were obtained from 51 patients with ESLD and 40 donor-recipient pairs. We analyzed the S-HLA-I in sera obtained from liver donors, as well as from liver transplant recipients (patients with ESLD), with sera from the latter obtained before and at various intervals up to 3 yr after transplantation. The results of the analyses justify the following conclusions: 1) Patients with ESLD had mean values of S-HLA-I (909 +/- 596 ng/ml) greater than those for the normal population (643 ng/ml) (P < 0.05); the S-HLA-I secretion decreased with increasing severity of liver disease. 2) Patients with tumors had mean S-HLA-I levels (399 ng/ml) significantly lower than those in patients with ESLD related to other causes. 3) In liver transplant recipients the S-HLA-I levels stabilized at approximately 1 month after transplant and remained relatively stable thereafter (mean level 950 +/- 536 ng/ml). The observed levels were also greater than those for the normal population (P < 0.05). 4) Preoperative and postoperative S-HLA-I values in liver transplant recipients demonstrated a biphasic distribution, dividing patients into high- and low-secretor groups. 5) During the post-transplant observation period, of these selected liver transplant recipients there was no difference between high- and low-secretor groups in the incidence of rejection (high, 70%; low, 67%), graft survival (high, 95%; low, 94%), or patient survival (high, 95%; low, 94%). 6) Measurement of the total amount of S-HLA-I, containing yet undefined ratios of both donor and recipient S-HLA-I, cannot be used to predict a state of tolerance in liver transplant recipients.