Intestine Transplantation Across a Positive Crossmatch With Preformed Donor-Specific Antibodies.

BACKGROUND: We describe our experience using a modified protocol for immunosuppression for intestine transplantation across a positive crossmatch. Patients who underwent transplantation in 2013 were evaluated over a 12-month period for rejection and infectious events with comparison to procedure-matched controls on our standard protocol of immunosuppression. PATIENTS AND METHODS: We used a modified protocol for intestine and multivisceral transplantation for patients with a positive flow crossmatch. In addition to our standard protocol, patients with positive crossmatch were given rituximab and intravenous immunoglobulin (IVIg) preoperatively. DSA was sent for clinical evaluation at monthly intervals. Patients were screened for rejection by endoscopic evaluation. RESULTS: Four patients underwent transplantation within a single year across a positive crossmatch. Two received isolated intestine transplants and 2 had multivisceral transplantation (MVT). During the 12-month follow-up, 1 patients had an episode of severe acute cellular rejection, which was managed with increased immunosuppression. None of the patients had episodes of cytomegalovirus infection. One patient developed major infection and 3 patients developed minor bacterial infections. Among procedure-matched controls with negative final crossmatch on standard management (no preoperative rituximab or IVIg), 2 developed mild acute cellular rejection and 2 developed minor infections. One developed cytomegalovirus viremia with invasion to the colonic mucosa. CONCLUSIONS: We report our protocol for immunosuppression for IT and MVT across a positive crossmatch. This allowed transplantation despite the presence of a positive crossmatch, with low rejection rates but potentially increased risk for major infections compared to the negative crossmatch controls on our standard protocol.

Influence of skinfold sum and peak VO(2) on immune function in children.

OBJECTIVE: To measure the relationship of skinfold sum and peak VO(2) power with immune function in children. DESIGN: Cross-sectional, with all children tested twice during a 2 month period for peak VO(2), sum of two skinfolds, and immune function, with data from the two measures averaged and then correlated (alpha level, < or = 0.01). Immune measures included leukocyte and lymphocyte subset counts, delayed-typed hypersensitivity (DTH), global IgG antibody response over 4 weeks to pneumococcal vaccination (pIgG), salivary IgA concentration (sIgA), PHA-stimulated lymphocyte proliferation (PHA-SLP), natural killer cell activity (NKCA), and granulocyte and monocyte phagocytosis and oxidative burst activity. SUBJECTS: Seventy-three children (n=42 males, n=31 females) ranging in age from 7 to 13 y (mean+/-s.d. age, 9.9+/-1.7 y). The mean skinfold sum was 28.9+/-17.1 mm, and peak VO(2) 45.8+/-8.1 ml/kg/min. RESULTS: Peak VO(2), skinfold sum, and immune measures did not differ significantly by age or gender. Therefore, correlations were made on combined indices for all subjects. Peak VO(2) and the skinfold sum were not significantly correlated with NKCA, oxidative burst activity, plgG or DTH. Peak VO(2) was negatively correlated with monocyte phagocytosis (r=-0.30, P=0.012) and positively correlated with PHA-SLP (6.25 microg/ml; r=0.35, P=0.004). The skinfold sum was positively correlated with the total leukocyte count (r=0.39, P<0.001), granulocyte count (r=0.36, P=0.002), monocyte count (r=0.38, P=0.001), monocyte phagocytosis (r=0.41, P<0.001), granulocyte phagocytosis (r=0.35, P=0.003), and sIgA (r=0.32, P=0.006), and negatively correlated with PHA-SLP (6.25 microg/ml; r=-0.39, P=0.001). CONCLUSIONS: Data from this study indicate that a high skinfold sum is related to elevated leukocyte subset counts and monocyte/granulocyte phagocytosis, and low PHA-SLP in children.

Change in salivary IgA following a competitive marathon race.

The influence of carbohydrate (1 l/h of a 6 % carbohydrate beverage), gender, and age on salivary IgA (sIgA) changes and incidence of upper respiratory tract infection (URTI) was studied in 98 runners following two competitive marathon races. The pattern of change in sIgA concentration differed significantly between carbohydrate (C) (N = 48) and placebo (P) (N = 50) groups, with higher post-race values measured in P. However, when this was adjusted for saliva protein concentration and saliva secretion rate, no difference between groups was measured. For all subjects combined, sIgA concentration, saliva IgA: protein ratio (spIgA), and sIgA secretion rates fell significantly (21 %, 31 %, and 25 %, respectively) below pre-race levels by 1,5-h post-race (p < 0.001). The pattern of change in all saliva measures did not differ significantly between the 12 women and 86 men in this study, and between the 23 older (> or =50 yr) and 75 younger (< 50 yr) subjects. Ninety-three subjects returned health/sickness logs, and of these, 16 (17 %) reported developing URTI during the 15-d period following the race event. The 1.5-h post-race spIgA concentration, but not sIgA concentration or secretion rate, was lower in runners reporting URTI compared to those who did not (254 +/- 30 and 388 +/- 26 microg*g(-1), respectively, p = 0.002), and this was negatively correlated with the post-race plasma cortisol concentration (r = -0.36, p < 0.001). Of the 16 runners, six were in the C group and 10 in the P group (Chi square = 1.11, p = 0.293). In conclusion, the output of sIgA decreased in runners following a competitive marathon, and this was not influenced by carbohydrate ingestion, age, or gender.

Influence of carbohydrate on cytokine and phagocytic responses to 2 h of rowing.

PURPOSE: This study examined the influence of carbohydrate (C) versus placebo (P) beverage ingestion on the phagocytic and cytokine responses to normal rowing training by 15 elite female rowers. METHODS: Athletes received C or P before, during and after, two, 2-h bouts of rowing performed on consecutive days. Blood was collected before and 5-10 min and 1.5 h after rowing. Metabolic measures indicated that training was performed at moderate intensities, with some high-intensity intervals interspersed throughout the sessions. RESULTS: Concentrations of blood neutrophils and monocytes, phagocytic activity, and plasma IL-1ra were significantly lower postexercise after C versus P ingestion. No differences were observed for oxidative burst activity, IL-6, IL-8, or TNFalpha. Glucose was significantly higher after 2 h of rowing with C ingestion; however, cortisol, growth hormone, epinephrine, norepinephrine, and CRP were not affected by carbohydrate. CONCLUSIONS: These data indicate that carbohydrate compared with placebo ingestion attenuated the moderate rise in blood neutrophils, monocytes, phagocytosis, and plasma IL-1ra concentrations that followed 2-h bouts of training in elite female rowers. No changes in blood hormone concentrations were found.

Reproductive, neuroendocrine, and immune consequences of acute exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in the Siberian hamster.

The present study tested the hypothesis that acute treatment with 2, 3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) impairs fertility, disrupts the nocturnal melatonin rhythm, and suppresses lymphocyte function. Adult Siberian hamsters administered 2 or 100 microg TCDD/kg body weight/0.2 ml sesame oil had a delayed latency to first litter and an increased adult mortality compared to hamsters given 0.1 microg/kg or vehicle. Within 75 days of TCDD treatment, full reproductive capabilities were achieved. Moreover, the nocturnal melatonin rhythm was not disrupted in adults administered TCDD or in their progeny. Lymphocyte activity varied with respect to time of day and treatment. Lymphocyte proliferation was enhanced at night irrespective of TCDD treatment; during the day, 2 wk after the 2-microg/kg treatment, blastogenesis was reduced compared to that in the 0.1-microg/kg group or in vehicle-treated controls. In contrast, TCDD did not affect the mixed lymphocyte reaction in response to allogeneic antigen when assessed at 2 and 20 wk post-treatment. Thus, findings indicate that TCDD produced acute effects on fertility, mortality, and systemic lymphocyte proliferation, but long-lasting effects on specific aspects of reproductive, neuroendocrine, and immune cell functions were not observed.

Immune function in female elite rowers and non-athletes.

OBJECTIVE: To compare immune function in female rowers and controls in the resting state, and then correlate the results with a two month history of upper respiratory tract infection (URTI). METHODS: Subjects included 20 elite female rowers located at the ARCO Olympic Training Centre in Chula Vista, California, and 19 non-athletic female controls. These two groups were compared cross sectionally for immune function and infection rates. RESULTS: Granulocyte/monocyte phagocytosis, oxidative burst activity, and plasma cytokine concentrations (interleukin-6, tumour necrosis factor-alpha, and interleukin-1 receptor antagonist) did not differ significantly between groups. Phytohaemagglutinin induced lymphocyte proliferative response (adjusted whole blood method) was significantly higher (31% and 36% for optimal and suboptimal concentrations respectively) in rowers than in controls. Natural killer cell activity was substantially higher (1.6-fold for total lytic units) in the female rowers than in controls. Two month health logs disclosed 5.2 (1.2) and 3.3 (1.1) days with URTI symptoms for the rowers and controls respectively (p = 0.268). For all 39 subjects combined, and for the 20 rowers separately, none of the immune parameters correlated significantly with number of days with URTI symptoms. CONCLUSIONS: In this cross sectional comparison of elite female rowers and non-athletes, a group difference was found for natural killer cell activity and phytohaemagglutinin induced proliferative response (whole blood technique), but not other measures of immune function. The number of days with URTI symptoms during the spring season did not differ between groups, and variations in blood measures of immunity were unrelated to URTI.

Saliva immunoglobulins in elite women rowers.

Saliva immunoglobulins (sIgA, sIgG, and sIgM) and upper respiratory tract infection (URTI) rates were evaluated in 20 elite female rowers and 19 nonathletes. Also, the influence of carbohydrate versus placebo beverage consumption on saliva immunoglobulin responses to rowing training sessions was measured in 15 rowers and in 5 non-exercising rowers. Saliva samples were collected 1 day before, and 5-10 min and 1.5 h after rowing or rest. Pre-exercise sIgA (but not sIgG or sIgM) concentration was 77% higher in the rowers compared to nonathletes (P < 0.001). Health records kept over 2 months revealed mean 5.2 (SEM 1.2) and 3.3 (SEM 1.1) days with URTI symptoms for the rowers and controls, respectively. For all 39 subjects, and for the 20 rowers separately, no significant correlation was found between URTI symptoms or insulin, cortisol, and growth hormone concentrations and pre-exercise or exercise-related changes in saliva immunoglobulin concentrations or secretion rates. The patterns of change in saliva immunoglobulin concentration and secretion rate did not differ between the carbohydrate and placebo rowing trials, or between exercised and rested athletes. These data indicated an increased sIgA concentration in the female elite rowers compared to the nonathletes, no association between saliva immunoglobulins and URTI, and no effect of a normal 2-hour training session or carbohydrate ingestion on saliva immunoglobulin concentrations or secretion rates.

Maturation of lymphocyte immunophenotypes and memory T helper cell differentiation during development in mice.

The goal of this study was to systematically investigate the ontogeny of lymphoid populations throughout postnatal development. In CD-1 mice, peak lymphocyte numbers occurred in blood on postnatal day 10 (d10) including those for natural killers (NK1.1), B cells (CD19), T helper (CD3CD4), naïve T helper (CD4CD62LposCD44low), memory T helper (CD4CD62LnegCD44high), and T cytotoxic (CD3CD8) cells. As percent of total lymphocytes, peaks were achieved by d10 for all T helper subtypes but not B cells which declined to a nadir. In spleen, lymphocyte numbers increased exponentially after d10. Proportionately, NK and T cells peaked on d10, declined by d20, and increased 2-3-fold by d45. Naive T cells constituted the majority of lymphocytes during development while memory cells gained to 2.2% (blood) and 12% (spleen) by d20. C57BL/6 mice had similar profiles except that the B cell nadir and T cell subset peaks were at d5. Peripheralization of critical numbers of lymphocytes by d10, and importantly, development of a repertoire of memory cells by d20, may define immune response capabilities that close the period of immaturity for the neonate.

Role of photoperiod and the pineal gland in T cell-dependent humoral immune reactivity in the Siberian hamster.

The present study tested the hypothesis that antibody production in response to xenoantigen is modulated by daylength and dependent upon the pineal gland. Alter injection of sheep erythrocytes (SRBC), serum immunoglobulin (Ig) concentrations were 5-fold lower in hamsters in short versus long days. Pinealectomy (Pinx) abolished the nocturnal melatonin rhythm, blocked short-day-mediated testis regression, and eliminated the short-day reduction in Ig production after SRBC treatment. Antibody titers in response to SRBC were equivalently augmented in short-day Pinx and long-day sham hamsters. The results indicate that photoperiodic effects on T cell-dependent humoral immunity are dependent upon the pineal gland. These findings raise the possibility that day length-associated changes in some immune system functions are mediated by the pineal melatonin rhythm.

Immune response to two hours of rowing in elite female rowers.

The influence of carbohydrate (C) versus placebo (P) beverage consumption on the immune and hormonal responses to normal rowing training sessions was measured in 15 elite female rowers residing at the U.S. Olympic Training Center. In a randomized, counterbalanced design, the athletes received C or P beverages (double-blind) before, during, and after two 2-hour bouts of rowing (one day apart). Blood samples were collected before, and 5-10 minutes and 1.5 hours after rowing. Metabolic measures indicated that training was performed at moderate intensities, with some high intensity intervals interspersed throughout the sessions (mean oxygen uptake of 2,307+/-169 m x min(-1), 57% of VO2max). Glucose and insulin were significantly lower after two hours of rowing with ingestion of P compared to C. The patterns of change in cortisol, growth hormone, epinephrine, and norepinephrine did not differ between C and P rowing trials. Blood neutrophil cell counts and the neutrophililymphocyte ratio were significantly higher following P versus C rowing sessions. The patterns of change in blood lymphocyte and lymphocyte subset counts, and lymphocyte proliferative responses did not differ between P and C trials, except for a slight difference in NK cell counts and activity. In summary, minimal changes in blood hormonal and immune measures were found following two-hour bouts of training in elite female rowers. Carbohydrate compared to placebo ingestion attenuated the moderate rise in blood neutrophil counts, but had slight or no effects on other immune parameters.

Influence of exercise mode and carbohydrate on the immune response to prolonged exercise.

The influence of exercise mode and 6% carbohydrate (C) versus placebo (P) beverage ingestion on lymphocyte proliferation, natural killer cell cytotoxicity (NKCA), Interleukin (IL)-1beta production, and hormonal responses to 2.5 hr of intense running and cycling (approximately 75% VO2max) was measured in 10 triathletes serving as their own controls. The C versus P condition (but not exercise mode) resulted in higher plasma glucose concentrations, lower plasma cortisol concentrations, reduced postexercise lymphocytosis and NKCA, and a lessened T-cell reduction during recovery, No condition or mode effects were observed for concanavalin A and phytohemagglutinin-induced lymphocyte proliferation. Significant mode (but not condition) effects were observed for lipopolysaccharide-induced IL-1beta production over time. However, when expressed per monocyte, the mode effect was abolished and a sustained suppression in IL-1beta/monocyte was observed in all sessions throughout recovery. These data indicate that carbohydrate ingestion significantly affects plasma glucose and cortisol concentrations, blood lymphocyte counts, and NKCA, whereas exercise mode has no effect on these parameters.

Influence of obesity on immune function.

OBJECTIVE: To compare immune function in obese and nonobese subjects. DESIGN: Obese and nonobese subjects were compared cross-sectionally. To test for the influence of other factors on immunity, aerobic fitness, psychological well-being, and serum levels of glucose, triglycerides, and cholesterol were measured and included in multiple regression models to determine their comparative effects. SUBJECTS/SETTING: Community-based subjects included 116 obese women (age = 44.3 +/- 9.7 years, body mass index = 33.2 +/- 6.5) and 41 nonobese women (age = 42.2 +/- 10.9 years, body mass index = 21.2 +/- 1.9). STATISTICAL ANALYSES PERFORMED: Independent t tests, Pearson product moment correlations, and stepwise multiple regression procedures. RESULTS: Obesity was linked to elevated leukocyte and lymphocyte subset counts (except for natural killer and cytotoxic/suppressor T cells), suppressed mitogen-induced lymphocyte proliferation (an index of T- and B-cell function), higher monocyte and granulocyte phagocytosis and oxidative burst activity, and normal activity of natural killer cells. APPLICATIONS/CONCLUSIONS: These data support the contention that obesity is associated with alterations in immune function. Further research is needed to link immunosuppression with the previously reported elevated risk of infection among the obese.

Influence of photoperiod on immune cell functions in the male Siberian hamster.

The present study tested the hypothesis that immune cell function is influenced by ambient photoperiod. The male Siberian hamster served as the experimental model because day length regulates a variety of seasonal adaptations in physiology. Adult hamsters were in long days (16 h of light daily), which sustains gonadal function, or transferred to short days (8 h) for >4 wk to induce testes regression. Blood was drawn from the ocular sinus or splenocytes obtained to assess basal indexes of immune cell function. In hamsters in short days, natural killer cell cytolytic capacity, as well as spontaneous blastogenesis in both whole blood and isolated lymphocytes, were enhanced compared with that in hamsters in long days. By contrast, phagocytosis and oxidative burst activity by both granulocytes and monocytes were suppressed in hamsters by exposure to short days versus long days. Selective changes in immune cell function coincided with short-day-induced gonadal atrophy. These findings raise the hypothesis that photoperiod regulation of physiological adaptations, including distinct immune cell functions, may help individuals anticipate seasonal challenges posed by opportunistic diseases or climate to facilitate survival.

Effects of mode and carbohydrate on the granulocyte and monocyte response to intensive, prolonged exercise.

The influence of exercise mode and 6% carbohydrate (C) vs. placebo (P) beverage ingestion on granulocyte and monocyte phagocytosis and oxidative burst activity (GMPOB) after prolonged and intensive exertion was measured in 10 triathletes. The triathletes acted as their own controls and ran or cycled for 2.5 h at approximately 75% maximal O2 uptake, ingesting C or P (4 total sessions, random order, with beverages administered in double-blind fashion). During the 2. 5-h exercise bouts, C or P (4 ml/kg) was ingested every 15 min. Five blood samples were collected (15 min before exercise, immediately after exercise, and 1.5, 3, and 6 h after exercise). The pattern of change over time for GMPOB was significantly different between C and P conditions (P

Influence of mode and carbohydrate on the cytokine response to heavy exertion.

OBJECTIVE AND METHODS: This randomized, double-blind, placebo-controlled study was designed to determine the influence of exercise mode and 6% carbohydrate (C) versus placebo (P) beverage ingestion, on blood cell counts, plasma glucose, hormone, and inflammatory cytokine responses (five total samples over 9 h) to 2.5 h of high-intensity running and cycling (approximately 75% VO2max) by 10 triathletes who acted as their own controls. Statistical significance was set at P < or = 0.05. RESULTS: C relative to P ingestion (but not exercise mode) was associated with higher plasma levels of glucose and insulin, lower plasma cortisol and growth hormone, and diminished perturbation in blood immune cell counts. The pattern of change over time for interleukin (IL)-6 was significantly different between C and P conditions (P = 0.021) and between running and cycling modes (P < 0.001), with the lowest postexercise values seen in the C-cycling sessions (10.7 +/- 1.8 pg x mL(-1)) and the highest in the P-running sessions (51.6 +/- 14.2 pg x mL(-1)). The pattern of change over time between C and P conditions (but not modes) was significantly different for IL-1 receptor antagonist (P = 0.003), with values once again lowest for the C-cycling sessions (1.5 h postexercise, 301 +/- 114 pg x mL(-1)) and highest for the P-running sessions (1171 +/- 439 pg x mL(-1)). CONCLUSION: These data indicate that carbohydrate versus placebo ingestion (4 mL x kg(-1) carbohydrate or placebo every 15 min of the 2.5-h exercise bout) is associated with higher plasma glucose levels, an attenuated cortisol response, and a diminished pro- and anti-inflammatory cytokine response.

Immune response to exercise training and/or energy restriction in obese women.

PURPOSE: The effect of exercise training (five 45-min walking sessions/wk at 60-75% maximum heart rate) and/or moderate energy restriction (4.19-5.44 MJ or 1,200-1,300 kcal x d(-1)) on innate and adaptive immunity (including mitogen-stimulated lymphocyte proliferation (MSLP), natural killer cell activity (NKCA), and monocyte and granulocyte phagocytosis and oxidative burst (MGPOB) was studied in obese women (N = 91, age 45.6 +/- 1.1 yr, body mass index 33.1 +/- 0.6 kg x m(-2)) randomized to one of four groups: control (C), exercise (E), diet (D), exercise, and diet (ED). METHODS: Aerobic power, body composition, and immune function were measured in all subjects before and after a 12-wk diet intervention period, with data analyzed using a 4 x 2 repeated measures design. All subjects self-reported symptoms of sickness in health logs using a precoded checklist. Statistical significance was set at P < or = 0.05. RESULTS: Data from this study indicate that although exercise training was unrelated to any significant changes in resting immune function, the number of days with symptoms of upper respiratory tract infection (URTI) was reduced relative to subjects in the nonexercise groups (5.6 +/- 0.9 and 9.4 +/- 1.1 sickness days, respectively, P < 0.05). Energy restriction and weight loss (7.9 +/- 0.7 kg) was associated with a significant decrease in MSLP, but no change in NKCA, MGPOB, or URTI. CONCLUSION: The data are consistent the viewpoint that weight loss, even at a moderate rate, is associated with a decrease in mitogen-stimulated lymphocyte proliferation without a change in various measures of innate immunity of the blood compartment.