The detection of specific antibody formation to recall antigens after human bone marrow transplantation

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 582-587 ◽  
Author(s):  
LG Lum ◽  
NA Munn ◽  
MS Schanfield ◽  
R Storb

The results of this study show that donor-derived immunity can be detected and persists in long-term survivors with and without chronic graft-v-host disease (GVHD) after human marrow grafting. Seventy-one marrow recipients (60 long-term and 11 short-term survivors) were studied for the presence of specific serum IgG antibodies to tetanus toxoid (TT), and 46 marrow recipients (35 long-term and 11 short-term) were tested for antibodies to diphtheria toxoid (DT) and measles virus after marrow grafting using an enzyme-linked immunosorbent assay. Of the 60 long-term survivors, 31 were healthy and 29 had chronic GVHD. None of the recipients were immunized to the test antigens postgrafting. Most long-term healthy recipients exhibited antibody titers to the recall test antigens, whereas only a minority of those with chronic GVHD had antibody titers to recall antigens. In healthy long-term recipients (greater than or equal to one year postgrafting) whose donors were immune to the test antigens, 25 of 31 had titers to TT, 11 of 17 had titers to DT, and 12 of 20 had titers to measles. In recipients with C-GVHD, 13 of 29 had titers to TT, six of 15 had titers to DT, and six of 15 had titers to measles virus. Within 100 days postgrafting, 11 of 11 had anti-TT titers, ten of ten had anti-DT titers, and seven of eight had antimeasles virus titers.

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 582-587 ◽  
Author(s):  
LG Lum ◽  
NA Munn ◽  
MS Schanfield ◽  
R Storb

Abstract The results of this study show that donor-derived immunity can be detected and persists in long-term survivors with and without chronic graft-v-host disease (GVHD) after human marrow grafting. Seventy-one marrow recipients (60 long-term and 11 short-term survivors) were studied for the presence of specific serum IgG antibodies to tetanus toxoid (TT), and 46 marrow recipients (35 long-term and 11 short-term) were tested for antibodies to diphtheria toxoid (DT) and measles virus after marrow grafting using an enzyme-linked immunosorbent assay. Of the 60 long-term survivors, 31 were healthy and 29 had chronic GVHD. None of the recipients were immunized to the test antigens postgrafting. Most long-term healthy recipients exhibited antibody titers to the recall test antigens, whereas only a minority of those with chronic GVHD had antibody titers to recall antigens. In healthy long-term recipients (greater than or equal to one year postgrafting) whose donors were immune to the test antigens, 25 of 31 had titers to TT, 11 of 17 had titers to DT, and 12 of 20 had titers to measles. In recipients with C-GVHD, 13 of 29 had titers to TT, six of 15 had titers to DT, and six of 15 had titers to measles virus. Within 100 days postgrafting, 11 of 11 had anti-TT titers, ten of ten had anti-DT titers, and seven of eight had antimeasles virus titers.


Blood ◽  
1987 ◽  
Vol 69 (1) ◽  
pp. 308-315 ◽  
Author(s):  
K Matsue ◽  
LG Lum ◽  
RP Witherspoon ◽  
R Storb

Upon activation, B cells express growth and differentiation receptors that permit them to proliferate and differentiate. The aim of this study is to define the nature of the intrinsic B cell defects found in marrow recipients using assays for B cell activation, proliferation, and differentiation. B cells from five short-term (less than three months postgrafting) and 15 long-term (greater than one year postgrafting) marrow recipients (ten with and five without chronic graft-v -host disease [GVHD]) were studied. T cell supernatants (T-sup) were prepared by stimulating normal T cells with 12–0-tetradecanoyl- phorbol-13-acetate (TPA) and phytohemagglutinin. Highly purified B cells were used to assess B cell proliferation responses to T-sup after Staphylococcus aureus Cowan I (SAC) activation and for B cell immunoglobulin production responses to T-sup stimulation after SAC activation. B cells from all five short-term patients and one long-term patient with chronic GVHD did not respond to any stimulation. B cells from two patients with chronic GVHD responded to SAC but had decreased proliferative and differentiative responses to T-sup. B cells from three of seven patients with chronic GVHD and two of five long-term healthy patients could proliferate but could not secrete immunoglobulin in response to SAC plus T-sup stimulation. Furthermore, there was a significant correlation between serum IgG and/or IgM in marrow recipients and the differentiative responses of their B cells to T-sup (P = 0.0075, Fisher's Exact). B cell defects occur at various stages of maturation postgrafting. These defects include the failure to respond to the SAC activation signal, the failure to proliferate in response to T-sup, and the failure to differentiate in response to T-sup. These findings are probably due to the inability of B cells from certain marrow recipients to undergo a second round of ontogeny.


Blood ◽  
1987 ◽  
Vol 69 (1) ◽  
pp. 308-315 ◽  
Author(s):  
K Matsue ◽  
LG Lum ◽  
RP Witherspoon ◽  
R Storb

Abstract Upon activation, B cells express growth and differentiation receptors that permit them to proliferate and differentiate. The aim of this study is to define the nature of the intrinsic B cell defects found in marrow recipients using assays for B cell activation, proliferation, and differentiation. B cells from five short-term (less than three months postgrafting) and 15 long-term (greater than one year postgrafting) marrow recipients (ten with and five without chronic graft-v -host disease [GVHD]) were studied. T cell supernatants (T-sup) were prepared by stimulating normal T cells with 12–0-tetradecanoyl- phorbol-13-acetate (TPA) and phytohemagglutinin. Highly purified B cells were used to assess B cell proliferation responses to T-sup after Staphylococcus aureus Cowan I (SAC) activation and for B cell immunoglobulin production responses to T-sup stimulation after SAC activation. B cells from all five short-term patients and one long-term patient with chronic GVHD did not respond to any stimulation. B cells from two patients with chronic GVHD responded to SAC but had decreased proliferative and differentiative responses to T-sup. B cells from three of seven patients with chronic GVHD and two of five long-term healthy patients could proliferate but could not secrete immunoglobulin in response to SAC plus T-sup stimulation. Furthermore, there was a significant correlation between serum IgG and/or IgM in marrow recipients and the differentiative responses of their B cells to T-sup (P = 0.0075, Fisher's Exact). B cell defects occur at various stages of maturation postgrafting. These defects include the failure to respond to the SAC activation signal, the failure to proliferate in response to T-sup, and the failure to differentiate in response to T-sup. These findings are probably due to the inability of B cells from certain marrow recipients to undergo a second round of ontogeny.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5163-5163
Author(s):  
Takao Yoshihara ◽  
Akira Morimoto ◽  
Hiroshi Kuroda ◽  
Hiroyuki Ishida ◽  
Toshihiko Imamura ◽  
...  

Abstract The long-term presence of fetal hematopoietic cells in the maternal blood after childbirth indicates maternal tolerance to fetal inherited paternal antigens (IPA), and also that of maternal hematopoietic cells in the offspring’s blood after birth indicates mutual tolerance to non-inherited maternal antigens (NIMA) among sibling. Based on such recent feto-maternal microchimerism / tolerance theory, more than 40 cases have received non-T-cell-depleted (non-TCD) HLA-haploidentical stem cell transplantation (SCT) for various hematological malignancies in Japan. Their early post-SCT clinical courses have been reported; however, long-term outcome and quality of life of such SCT recipients are largely unknown. In our hospitals, we used non-TCD cells from haploidentical family donors for transplantation in 5 children with hematologic malignancies. Among those children, four have been alive for more than one year. Three of the 4 recipients still require prophylactic immunosuppressants for chronic GVHD. Only one case developed chronic GVHD (skin limited). Various late complications are noted in 3. Three children showed complete school attendance. Two of the three are also allowed to participate in physical exercises. These results suggest that quality of life in long-term survivors in childhood from non-TCD HLA-haploidentical SCT based on feto-maternal microchimerism seems acceptable although the numbers are still small and the follow-up period is short. Patients characteristics Case Age Diagnosis Status Donor HLA mismatch acute GVHD Survival after SCT (days) 1 6 ALL CR1 (advanced remission) NIMA-mismatched sibling 2 2 CR, 802+ 2 11 ALL Rejection after UCBT (CR2) Mother 2 1 CR, 775+ 3 16 MLL Refractory relapse after UCBT Mother 2 1 CR, 519+ 4 14 CML Blastic phase Mother 2 1 CR, 473+ 5 6 ALL Rejection after UCBT (Rel 1) Mother 3 2 Dead, 93 Present status of long-term survivors Case chronic GVHD Karnofsky score Late complications School attendance Physical exercise Medication 1 - 100 - complete permitted - 2 - 100 hypothyroidism complete permitted FK506 3 + (skin) 70 diabetes, esophageal stricture no prohibited PSL+MTX, insulin 4 - 100 arrhythmia complete prohibited FK506


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2140-2140
Author(s):  
Faisal Khan ◽  
Sarah Sy ◽  
Polly Louie ◽  
Robyn Lee ◽  
Douglas A. Stewart ◽  
...  

Abstract Genomic Instability (GI), appraised by microsatellite length alteration, is a precancerous or cancerous condition. We hypothesized that genomic instability is frequent in oral but not nasal mucosal cells of HCT recipients as oral but not nasal carcinoma is frequent in long-term HCT survivors.We examined epithelial cells from buccal and nasal mucosa of 35 subjects for the presence of GI at 15 microsatellite loci spanning 14 human autosomes. The study population included long-term allo-HCT survivors (4–22 yrs, n=18) and short-term allo-HCT survivors (2–3 months, n=5), and long-term auto-HCT survivors (4–12 yrs, n=5). Controls also included 5 patients treated with intensive chemotherapy and 2 healthy volunteers. DNA extracted from peripheral blood leukocytes and cells of nasal and buccal mucosa was PCR amplified for a panel of 15 Short tandem repeat (STR) markers (ABI-Identifiler TM). The amplicons were subjected to capillary electrophoresis and fragment size analysis was performed to identify novel allele peaks (one that was absent in donor and recipient blood pre-transplant but present in recipient mucosa post-transplant) indicative of microsatellite instability (MSI). MSI was observed in buccal mucosal cells of 56% long-term survivors of allo-HCT; the number of STR loci showing novel allele peaks ranged from 1–6 (median=3). None of the short-term survivors of allo-HCT, long-term survivors of auto-HCT, or control individuals showed MSI in the buccal mucosal cells. Only one allogeneic HCT survivor showed MSI (at one STR locus) in nasal mucosal cells. No genomic alterations were observed in blood leukocytes of any of the above patients or controls. In conclusion, genomic instability is frequently observed in long-term allo-HCT suvivors in oral mucosal cells but rarely in nasal mucosal cells. The facts that oral but not nasal mucosa is frequently involved in chronic GVHD and that MSI was not detected in recipients of auto-HCT suggest that graft-vs-host reaction induces genomic instability.


1989 ◽  
Vol 22 (1) ◽  
pp. 25-29 ◽  
Author(s):  
Alexandre C. Linhares ◽  
Valéria R. Melo ◽  
Joana D'Arc P. Mascarenhas ◽  
Yvone B. Gabbay ◽  
Ronaldo B. de Freitas

Nine hundred and forty-eight serum samples from 83 children living in Belem, Brazil, collected'within their first three years of life, were testedfor the presence of group- specific rotavirus-antibody by an enzyme-linked immunosorbent assay (ELISA) blocking-test. Passively transferred maternal antibody lasted about two and half months; subsequentely, low levels of rotavirus antibody started to appear at seven months, reaching a peak at eleven months of age. From one year onwards positivity gradually increased, reaching highest values at 34 months of life. Individual responses were examined in sera from 61 children who were followed up since birth to three years of age: 38 (62,3%) ofthem developed a long-term immunity following first infection; eleven (18.0%) children developed a short-term immunity after first infection by rotavirus; seven (11.5%) had no antibody response within their first three years of life; and 5 (8.2%) showed positive antibody response from birth to three years old.


2021 ◽  
Vol 12 ◽  
Author(s):  
Tiandan Xiang ◽  
Boyun Liang ◽  
Yaohui Fang ◽  
Sihong Lu ◽  
Sumeng Li ◽  
...  

Major advances have been made in understanding the dynamics of humoral immunity briefly after the acute coronavirus disease 2019 (COVID-19). However, knowledge concerning long-term kinetics of antibody responses in convalescent patients is limited. During a one-year period post symptom onset, we longitudinally collected 162 samples from 76 patients and quantified IgM and IgG antibodies recognizing the nucleocapsid (N) protein or the receptor binding domain (RBD) of the spike protein (S). After one year, approximately 90% of recovered patients still had detectable SARS-CoV-2-specific IgG antibodies recognizing N and RBD-S. Intriguingly, neutralizing activity was only detectable in ~43% of patients. When neutralization tests against the E484K-mutated variant of concern (VOC) B.1.351 (initially identified in South Africa) were performed among patients who neutralize the original virus, the capacity to neutralize was even further diminished to 22.6% of donors. Despite declining N- and S-specific IgG titers, a considerable fraction of recovered patients had detectable neutralizing activity one year after infection. However, neutralizing capacities, in particular against an E484K-mutated VOC were only detectable in a minority of patients one year after symptomatic COVID-19. Our findings shed light on the kinetics of long-term immune responses after natural SARS-CoV-2 infection and argue for vaccinations of individuals who experienced a natural infection to protect against emerging VOC.


2002 ◽  
Vol 27 (1) ◽  
pp. 13-20 ◽  
Author(s):  
Sanjay Sehgal ◽  
I Balakrishnan

The study attempts to evaluate if there are any systematic patterns in stock returns for the Indian market. The empirical findings reveal that there is a reversal in long-term returns, once the short-term momentum effect has been controlled by maintaining a one year gap between portfolio formation period and the portfolio holding period. A contrarian strategy based on long-term past returns provides moderately positive returns. Further, there is a continuation in short-term returns and a momentum strategy based on it provides significantly positive payoffs. The results in general are in conformity with those for developed capital markets such as the US.


2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Ana Isabel Penzlin ◽  
Kristian Barlinn ◽  
Ben Min-Woo Illigens ◽  
Kerstin Weidner ◽  
Martin Siepmann ◽  
...  

2003 ◽  
Vol 25 (3) ◽  
pp. 103-114 ◽  
Author(s):  
Harald Blegen ◽  
John S. Will ◽  
B. Michael Ghadimi ◽  
Hesed‐Padilla Nash ◽  
Anders Zetterberg ◽  
...  

In order to explore whether specific cytogenetic abnormalities can be used to stratify tumors with a distinctly different clinical course, we performed comparative genomic hybridization (CGH) of tumors from patients who were diagnosed with metastatic disease after an interval of less than 2 years or who remained free from distant metastases for more than 10 years. All patients presented with distant metastases after mastectomy indicating that none of the patients in this study was cured and free of remaining tumor cells. Tumors in the group of short‐term survivors showed a higher average number of chromosomal copy alterations compared to the long‐term survivors. Of note, the number of sub‐chromosomal high‐level copy number increases (amplifications) was significantly increased in the group of short‐term survivors. In both short‐ and long‐term survivors recurrent chromosomal gains were mapped to chromosomes 1q, 4q, 8q, and 5p. Copy number changes that were more frequent in the group of short‐term survivors included gains of chromosome 3q, 9p, 11p and 11q and loss of 17p. Our results indicate that low‐ and high grade malignant breast adenocarcinomas are characterized by a specific pattern of chromosomal copy number changes. Furthermore, immunohistochemical evaluation of the expression levels of Ki‐67, p27KIP1, p21WAF1, p53, cyclin A and cyclin E revealed a correlation between increased proliferative activity and poor outcome.


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