Patients Who Respond to Donor Lymphocyte Infusion (DLI) Have an Antibody Response Against PDC-E2, the Immunodominant Autoantigens of Primary Biliary Cirrhosis (PBC), but with Different Specificity.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3105-3105
Author(s):  
Roberto Bellucci ◽  
Meagan Gallagher ◽  
Sabine Oertelt ◽  
Emmanuel Zorn ◽  
Edwin P. Alyea ◽  
...  
Keyword(s):  
Liver Disease ◽  
Antibody Response ◽  
High Titer ◽  
Hematologic Malignancies ◽  
Donor Lymphocyte Infusion ◽  
Antibody Responses ◽  
Biliary Cirrhosis ◽  
Allogeneic Hsct ◽  
Inner Lipoyl Domain ◽  
Lipoyl Domain

Abstract Although, the effectiveness of allogeneic hematopoietic stem cell transplantation (HSCT) is, in large part, due to the destruction of recipient malignant cells by donor immune cells, the antigenic targets of this response in most patients are not well defined. In previous studies we demonstrated that patients with multiple myeloma (MM) who achieved a complete response after HSCT and donor lymphocyte infusion (DLI) developed high titer antibodies to a variety of antigens expressed by myeloma cells. Dihydrolipoamide acetyltransferase, the E2 component of the pyruvate dehydrogenase complex (PDC-E2) was one of the antigens identified in this screen. Importantly PDC-E2 is the immunodominant auto-antigen in primary biliary cirrhosis (PBC), a liver autoimmune disease in which greater than 95% of patients develop auto-antibodies against the inner lipoyl domain of this mitochondrial antigen. To further characterize the antibody response against PDC-E2 after allogeneic HSCT, we developed a sensitive ELISA to measure antibody responses to GST-PDC-E2 fusion protein. PDC-E2 antibodies following HSCT were compared to 52 normal donors and 50 patients with PBC. All samples were tested at 1:50 or 1:100 dilution. PDC-E2 antibodies were not detected in 20 patients with MM at the time of diagnosis, 10 patients with hematologic malignancies after allogeneic HSCT who did not receive DLI and 10 patients with chronic graft-versus-host disease (GVHD). However, when screening patients who achieved complete remission after DLI, PDC-E2 antibodies were detecting in 3 out of 10 patients with MM, 1 out of 5 patients with chronic myelocytic leukemia (CML) and 1 out of 2 patients with chronic lymphocytic leukemia (CLL). Although some of these patients developed GVHD, none developed chronic liver disease. In each case, PDC-E2 antibodies were only detectable after DLI and not pre-HSCT or pre-DLI. In 2 patients with particulary high titer antibodies (detectable down to 1:10,000 dilution) anti-PDC-E2 persisted for more than 2 years post-DLI and the dominant Ig subclasses at all time points were IgG1 and IgG2. The specificity of PDC-E2 antibodies post-DLI was also tested by ELISA against a panel of 85 overlapping peptides representing the entire amino acid sequence of PDC-E2 and by western blot against 2 common mitochondrial auto-antigens, branched-chain alpha-keto acid dehydrogenase (BCKD) and 2-oxoglutarate dehydrogenase (ODGC). Post-DLI sera were not reactive with BCKD or ODGC and most samples specifically recognized 2 peptides located in the E2 catalytic domain of PDC-E2. In contrast, serum from PBC patients had a different pattern of reactivity and were primarily directed against peptides in the inner lipoyl domain of PDC-E2. In conclusion, we demonstrate that patients with hematologic malignancies who achieve complete remission following DLI frequently develop allogeneic antibody responses directed against one of the most common auto-antigens in PBC. However, the epitope specificity of the antibody response following allogeneic HSCT is distinct and is not associated with chronic liver disease.

PDC-E2, a Common Auto Antigen in Primary Biliary Cirrhosis (PBC) Is Also a Target of an Antibody Response in Patients Who Achieve Complete Remission after Donor Lymphocyte Infusion.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2121-2121
Author(s):  
Roberto Bellucci ◽  
Meagan Gallagher ◽  
Hong-Nam Nguyen ◽  
Edwin P. Alyea ◽  
Emmanuel Zorn ◽  
...  
Keyword(s):  
T Cell ◽  
Primary Biliary Cirrhosis ◽  
Antibody Response ◽  
Pyruvate Dehydrogenase Complex ◽  
Cdna Expression Library ◽  
Biliary Cirrhosis ◽  
Allogeneic Bone ◽  
Antibody Reactivity ◽  
Inner Lipoyl Domain ◽  
Lipoyl Domain

Abstract The ability of donor lymphocyte infusions (DLI) to induce complete responses (CR) in patients with relapsed multiple myeloma (MM) following allogeneic bone marrow transplantation provides clear evidence of graft-versus-myeloma (GVM) immunity. To identify GVM associated target antigens, we previously screened an MM cDNA expression library with post DLI serum from 5 MM patients who achieved CR after DLI. One of the antigens identified in the screening was dihydrolipoamide acetyltranferase the E2 component of the pyruvate dehydrogenase complex (PDC-E2). Using a phage plate assay, antibody reactivity against PDC-E2 was found in 2 of 9 MM and 1 of 5 chronic myeloid leukemia (CML) patients who achieved a CR after DLI. No antibodies were found before DLI, in 20 normal donors, 10 patients who underwent T-cell depleted allogeneic BMT, 6 MM DLI non-responders and 20 patients with chronic GVHD. Primary biliary cirrhosis (PBC) is an autoimmune liver disease in which more than 80% of patients have autoantibodies against PDC-E2. In patients with PBC the major immunogenic epitope of PDC-E2 has been mapped to the region associated with the inner lipoyl domain. To better characterize the antibody response in MM patients who had a CR after DLI a GST-PDC-E2 fusion protein was purified and used to quantify the antibody response by ELISA. Using this sensitive assay we found 1 additional MM DLI responder who had antibody reactivity against PDC-E2. Analysis performed at serial time points after DLI showed that reactivity persisted for 1.5 and 3 years after DLI in two MM patients and 3 years after DLI in the CML DLI responder. To map the antibody response after DLI and compare this to antibody reactivity in patients with PBC, we synthesized a series of 85 overlapping peptides covering the entire length of PDC-E2 and analyzed the specificity of the antibody response by ELISA. Using this assay, post-DLI serum was found to be reactive against 4 peptides located in the E2 catalytic domain of PDC-E2 but no reactivity was detected against peptides located in the inner lipoyl domain of the protein, the region commonly recognized by auto-antibodies in PBC. Analysis of serial samples showed that the antibody response persisted against these peptides up to 2–3 years after DLI but no reactivity was found pre-DLI and in normal serum. In conclusion we show that PDC-E2, a common auto-antigen in the autoimmune disease PBC, is also the target of an antibody response in patients with MM and CML who achieve a CR after DLI. The antibody response found after DLI is directed against a different region of the protein. Further studies characterizing T cell epitopes in these patients are underway and they will help to better characterize the immune response against PDC-E2 in patients after DLI.

Allogeneic B Cell Response to H-Y Minor Histocompatibility Antigens after Donor Lymphocyte Infusion Correlates with Disease Response.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 296-296
Author(s):  
David B. Miklos ◽  
Katherine H. Miller ◽  
Haesook T. Kim ◽  
Stephanie J. Lee ◽  
Edwin P. Alyea ◽  
...  
Keyword(s):  
T Cell ◽  
Complete Remission ◽  
B Cell ◽  
Cell Response ◽  
High Titer ◽  
Donor Lymphocyte Infusion ◽  
Antibody Responses ◽  
Cell Responses ◽  
Male Patients ◽  
B Cell Responses

Abstract Donor lymphocyte infusion (DLI) can induce remission in many patients who relapse after allogeneic hematopoietic stem cell transplantation (HSCT). We have previously demonstrated that male HSCT patients with female donors frequently develop high-titer antibody responses to H-Y antigens that correlate with disease remission. DLI administered 6 months after T cell depleted HSCT results in a five-fold increase in peripheral B cell numbers. We sought to determine whether allogeneic B cell responses develop after DLI. We expressed 5 recombinant H-Y proteins (DBY, UTY, ZFY, RPS4Y and EIF1AY) and developed sensitive ELISA to quantify the development of specific anti-HY antibodies. First, we studied prophylactic DLI. Twenty-six patients who received T cell depleted HSCT followed 5–7 months later by prophylactic CD8 depleted DLI were tested for H-Y antibodies pre-DLI and 6–12 months after DLI. No H-Y antibodies were detected in any of the pre-DLI serum samples. However, all 6 male HSCT patients with female donors (F→M HSCT) developed high-titer antibodies against at least one H-Y antigen after DLI. In contrast, only 1/20 of the other donor/recipient gender combinations (4 M→M, 8 F→F, 8 M→F) resulted in H-Y antibody (p<0.005). Thus, mHA disparity is required for the development of allogeneic B cell responses after DLI. This robust development of H-Y antibody in 6/6 F→M patients who received TCD transplantation and prophylactic DLI was significantly greater than 3/9 who developed H-Y antibodies after receiving the same TCD HSCT without DLI (p=0.03). This suggests that DLI augments allogeneic B cell responses after T cell depleted HSCT. To examine the effects of therapeutic DLI, we studied 24 F→M HSCT patients who relapsed 60 days to 15 years (median 704 days) after transplant and subsequently received either unmanipulated DLI (1−3x107 CD3+ cells/kg; n=12) or CD8 depleted DLI (3x107 CD4+ cells/kg; n=12). Only 2/24 had any H-Y antibody at the time of relapse. After DLI, 17/24 (71%) developed antibody to at least one H-Y antigen, and this correlated with complete remission after DLI (p<0.001). Disease progression continued in all 7 patients who did not develop H-Y antibodies, but 15 of 17 patients who developed H-Y antibodies also attained complete remission. H-Y antibodies developed rapidly and were detected as early as 26 days after DLI. Fifteen of 17 patients (88%) became H-Y antibody positive before 150 days after DLI. In our previous study assessing HSCT alone, only 3 of 38 (8%) developed H-Y antibodies before 150 days. Complete remission was attained with similar frequencies after both CD8 depleted DLI (7/12) and unmanipulated DLI (8/12). However, significant differences were noted in H-Y antibody responses by DLI type. In contrast to unmanipulated DLI, patients receiving CD8 depleted DLI developed high-titer antibodies (p=0.045) against multiple H-Y antigens (p=0.012). In summary, H-Y antibodies frequently develop in male patients after infusion of female donor lymphocytes and this allogeneic B cell response correlates with clinical response to DLI. H-Y Antibody Results in Male Patients with Female Donors Any H-Y Antibody 2 or more H-Y Antibodies TCD HSCT + prophylactic CD8 depleted DLI 6/6 (100%) 4/6 (67%) TCD HSCT alone 3/9 (33%) 1/9 (11%) CD8 depleted DLI for relapse 9/12 (75%) 9/12 (75%) Unmanipulated DLI for relapse 8/12 (67%) 2/12 (17%)

scholarly journals Antibody Response to 2-Dose Sars-Cov-2 mRNA Vaccine in Allogeneic Hematopoietic Cell Transplant Recipients

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 336-336
Author(s):  
Alexis Maillard ◽  
Rabah Redjoul ◽  
Marion Klemencie ◽  
Hélène Labussière ◽  
Amandine Le Bourgeois ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Antibody Response ◽  
Antibody Responses ◽  
Hematopoietic Cell ◽  
Time Interval ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hsct ◽  
The Past

Abstract INTRODUCTION Immunocompromised patients have been excluded from initial trials evaluating SARS-CoV-2 mRNA vaccines and there is a critical need to warrant vaccine efficacy in hematopoietic stem cell transplant (HSCT) recipients. In this study, we evaluated antibody responses to 2 doses mRNA SARS-CoV-2 vaccine in allogeneic HSCT recipients. METHODS We retrospectively enrolled successive hematopoietic cell transplant recipients across France who completed the 2-dose SARS-CoV-2 mRNA vaccine (BNT162b2 or mRNA-1273) between January 1 st and July 15 th 2021. All included patients had an available semi-quantitative antispike serologic testing after the second dose (from Roche, DiaSorin, Abbott or Siemens). We excluded patients with a prior COVID-19 confirmed by serology or PCR. For detectable antibody, we calculated the binding antibody units per milliliter (BAU/mL) according to the WHO International Standard by applying conversion factors given by the manufacturers (Kristiansen et al. , The Lancet 2021). Antibody response was categorized as "weak" or "good" with a threshold of 264 BAU/mL which has been associated to an estimate of 80% of mRNA vaccine-induced protection against symptomatic COVID-19 in immunocompetent patients (Feng S. et al., medRxiv 2021). We built a multivariate logistic regression model to assess factors independently associated with the absence of antibody response after the second dose of mRNA vaccination. RESULTS Overall, 620 allogeneic HSCT recipients from 12 hospitals across France were included in the analysis (60% male with a median age of 59 years old [IQR 47-66]), most with a myeloid (69%) or lymphoid (26%) malignancies. Donors were matched unrelated for 51%, HLA-identical sibling for 31% and haplo-identical for 18%. Thirty-one percent of HSCT recipients underwent a myeloablative conditioning, while 69% received a reduced intensity conditioning. The two doses of vaccines were given one month apart and the median time between transplantation and the initiation of vaccination was 29 months [IQR 14-58]. At a median of 33 [IQR 27-50] days after dose 2, an antibody response was detectable in 496 patients (80% [95CI: 77 to 83%]). Median [IQR] antibody levels was 243 BAU/mL [29.4-1391]. We classified detectable antibody responses as "weak" in 189 patients (30% [95CI 27 to 34%]) and as "good" in 306 (49% [95CI: 45 to 53%]). In the multivariate analysis including 533 patients (420 with detectable antibodies), factors associated with the absence of humoral responses were a time-interval from HSCT < 12 months (ajusted Odds-Ratio (aOR) 2.8 [95CI 1.6 to 4.8]), absolute lymphocyte count <1G/L (aOR 3.0 [95CI 1.7 to 5.0]), systemic immunosuppressive treatments within 3 months of vaccination (aOR 4.5 [95CI 2.7 to 7.5]), together with the use of rituximab within 6 months (aOR 15.1 [95CI 4.3 to 52.7]). In a subsequent multivariate analysis conducted a subset of 227 patients (170 with detectable antibodies) with available gammaglobulinemia as well as B and T lymphocytes counts, factors remaining associated with the absence of antibody response were only low B-lymphocytes count (aOR 5.5 [95CI 2.4 to 12.3]) and time-interval from HSCT < 12 months (aOR 3.3 [95CI 1.5 to 7.2]). CONCLUSION After 2 dose mRNA vaccination, the majority of allogeneic HSCT recipients developed an antibody response although a significant proportion of these responses may be insufficient. Studies are still needed to investigate the effect of a third vaccine dose in patients with a null or weak humoral response. Disclosures Loschi: Servier: Ended employment in the past 24 months, Honoraria; Novartis: Ended employment in the past 24 months, Honoraria; Gilead: Ended employment in the past 24 months, Honoraria; AbbVie: Ended employment in the past 24 months, Honoraria; CELGENE/BMS: Honoraria; MSD: Honoraria.

scholarly journals Cellular therapy following allogeneic stem-cell transplantation

2011 ◽  
Vol 2 (6) ◽  
pp. 409-428 ◽  
Author(s):  
Alison Rager ◽  
David L. Porter
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cellular Therapy ◽  
Hematologic Malignancies ◽  
Donor Lymphocyte Infusion ◽  
Myelogenous Leukemia ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Relapsed Disease

Allogeneic hematopoietic stem-cell transplantation (HSCT) is the most effective approach for many patients with hematologic malignancies. Unfortunately, relapse remains the most common cause of death after allogeneic HSCT, and the prognosis of relapsed disease is poor for most patients. Induction of a graft- versus-leukemia (GVL), or graft- versus-tumor, effect through the use of donor leukocyte infusion (DLI), or donor lymphocyte infusion, has been remarkably successful for relapsed chronic myelogenous leukemia. Unfortunately, response to DLI in other hematologic malignancies is much less common and depends on many factors including histology, pace and extent of relapse, and time from HSCT to relapse. Furthermore, graft- versus-host disease (GVHD) is common after DLI and often limits successful immunotherapy. Ultimately, manipulations to minimize GVHD while preserving or enhancing GVL are necessary to improve outcomes for relapse after allogeneic HSCT.

scholarly journals NOD.c3c4 congenic mice develop autoimmune biliary disease that serologically and pathogenetically models human primary biliary cirrhosis

2006 ◽  
Vol 203 (5) ◽  
pp. 1209-1219 ◽  
Author(s):  
Junichiro Irie ◽  
Yuehong Wu ◽  
Linda S. Wicker ◽  
Daniel Rainbow ◽  
Michael A. Nalesnik ◽  
...  
Keyword(s):  
T Cells ◽  
Primary Biliary Cirrhosis ◽  
Pyruvate Dehydrogenase Complex ◽  
Biliary Cirrhosis ◽  
Biliary Disease ◽  
Nonobese Diabetic ◽  
Biliary Pathology ◽  
Biliary Ducts ◽  
Inner Lipoyl Domain ◽  
Lipoyl Domain

Primary biliary cirrhosis (PBC) is an autoimmune disease with a strong genetic component characterized by biliary ductular inflammation with eventual liver cirrhosis. The serologic hallmark of PBC is antimitochondrial antibodies that react with the pyruvate dehydrogenase complex, targeting the inner lipoyl domain of the E2 subunit (anti–PDC-E2). Herein we demonstrate that NOD.c3c4 mice congenically derived from the nonobese diabetic strain develop an autoimmune biliary disease (ABD) that models human PBC. NOD.c3c4 (at 9–10 wk, before significant biliary pathology) develop antibodies to PDC-E2 that are specific for the inner lipoyl domain. Affected areas of biliary epithelium are infiltrated with CD3+, CD4+, and CD8+ T cells, and treatment of NOD.c3c4 mice with monoclonal antibody to CD3 protects from ABD. Furthermore, NOD.c3c4-scid mice develop disease after adoptive transfer of splenocytes or CD4+ T cells, demonstrating a central role for T cells in pathogenesis. Histological analysis reveals destructive cholangitis, granuloma formation, and eosinophilic infiltration as seen in PBC, although, unlike PBC, the extrahepatic biliary ducts are also affected. Using a congenic mapping approach, we define the first ABD (Abd) locus, Abd1. These results identify the NOD.c3c4 mouse as the first spontaneous mouse model of PBC.

ANTIBODY RESPONSES TO NATURALLY OCCURRING POLIOMYELITIS INFECTIONS IN CHILDREN

PEDIATRICS ◽  
1955 ◽  
Vol 15 (4) ◽  
pp. 392-401
Author(s):  
C. Arden Miller ◽  
Jacqueline Baumeister
Keyword(s):  
Antibody Response ◽  
Clinical Diagnosis ◽  
Complement Fixation Test ◽  
Complement Fixation ◽  
High Titer ◽  
Antibody Responses ◽  
Fixation Test ◽  
Antigenic Structure ◽  
Tissue Cultures ◽  
Naturally Occurring

Serums collected over an 18-month period from children with a clinical diagnosis of poliomyelitis were studied by means of the complement fixation test. Test antigens were prepared from the nutrient fluid of tissue cultures infected with each of the 3 known types of poliomyelitis viruses. Results were compared with those obtained from neutralization tests on the same serums. The complement fixation test was of little diagnostic help in these patients; a high titer, a rise in titer, and a fall in titer were all inconstant findings. A complement fixing antibody titer persisting beyond 100 days was more indicative of the immunologic type of the infecting virus than any other feature of the complement fixing antibody response. The multitypic nature of the complement fixing antibody response was discussed in relation to the complex antigenic structure of poliomyelitis viruses.

scholarly journals Antibody response to SARS-CoV-2 vaccines in patients with hematologic malignancies

Cancer Cell ◽  
2021 ◽  
Author(s):  
Lee M. Greenberger ◽  
Larry A. Saltzman ◽  
Jonathon W. Senefeld ◽  
Patrick W. Johnson ◽  
Louis J. DeGennaro ◽  
...  
Keyword(s):  
Antibody Response ◽  
Hematologic Malignancies

scholarly journals From Multiplex Serology to Serolomics—A Novel Approach to the Antibody Response against the SARS-CoV-2 Proteome

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 749
Author(s):  
Julia Butt ◽  
Rajagopal Murugan ◽  
Theresa Hippchen ◽  
Sylvia Olberg ◽  
Monique van Straaten ◽  
...  
Keyword(s):  
Antibody Response ◽  
High Throughput ◽  
Large Population ◽  
High Sensitivity ◽  
Population Based ◽  
Antibody Responses ◽  
Hek293 Cells ◽  
Novel Approach ◽  
Assay Performance ◽  
Multiplex Serology

The emerging SARS-CoV-2 pandemic entails an urgent need for specific and sensitive high-throughput serological assays to assess SARS-CoV-2 epidemiology. We, therefore, aimed at developing a fluorescent-bead based SARS-CoV-2 multiplex serology assay for detection of antibody responses to the SARS-CoV-2 proteome. Proteins of the SARS-CoV-2 proteome and protein N of SARS-CoV-1 and common cold Coronaviruses (ccCoVs) were recombinantly expressed in E. coli or HEK293 cells. Assay performance was assessed in a COVID-19 case cohort (n = 48 hospitalized patients from Heidelberg) as well as n = 85 age- and sex-matched pre-pandemic controls from the ESTHER study. Assay validation included comparison with home-made immunofluorescence and commercial enzyme-linked immunosorbent (ELISA) assays. A sensitivity of 100% (95% CI: 86–100%) was achieved in COVID-19 patients 14 days post symptom onset with dual sero-positivity to SARS-CoV-2 N and the receptor-binding domain of the spike protein. The specificity obtained with this algorithm was 100% (95% CI: 96–100%). Antibody responses to ccCoVs N were abundantly high and did not correlate with those to SARS-CoV-2 N. Inclusion of additional SARS-CoV-2 proteins as well as separate assessment of immunoglobulin (Ig) classes M, A, and G allowed for explorative analyses regarding disease progression and course of antibody response. This newly developed SARS-CoV-2 multiplex serology assay achieved high sensitivity and specificity to determine SARS-CoV-2 sero-positivity. Its high throughput ability allows epidemiologic SARS-CoV-2 research in large population-based studies. Inclusion of additional pathogens into the panel as well as separate assessment of Ig isotypes will furthermore allow addressing research questions beyond SARS-CoV-2 sero-prevalence.

scholarly journals Antibody Responses in Cats Following Primary and Annual Vaccination against Feline Immunodeficiency Virus (FIV) with an Inactivated Whole-Virus Vaccine (Fel-O-Vax® FIV)

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 470
Author(s):  
Mark Westman ◽  
Dennis Yang ◽  
Jennifer Green ◽  
Jacqueline Norris ◽  
Richard Malik ◽  
...  
Keyword(s):  
Antibody Response ◽  
Virus Vaccine ◽  
Point Of Care ◽  
Primary Vaccination ◽  
Antibody Responses ◽  
Blood Samples ◽  
Study Results ◽  
Elisa Testing ◽  
Primary Antibody Response ◽  
Residual Blood

Although the antibody response induced by primary vaccination with Fel-O-Vax® FIV (three doses, 2–4 weeks apart) is well described, the antibody response induced by annual vaccination with Fel-O-Vax® FIV (single dose every 12 months after primary vaccination) and how it compares to the primary antibody response has not been studied. Residual blood samples from a primary FIV vaccination study (n = 11), and blood samples from cats given an annual FIV vaccination (n = 10), were utilized. Samples from all 21 cats were tested with a commercially available PCR assay (FIV RealPCRTM), an anti-p24 microsphere immunoassay (MIA), an anti-FIV transmembrane (TM; gp40) peptide ELISA, and a range of commercially available point-of-care (PoC) FIV antibody kits. PCR testing confirmed all 21 cats to be FIV-uninfected for the duration of this study. Results from MIA and ELISA testing showed that both vaccination regimes induced significant antibody responses against p24 and gp40, and both anti-p24 and anti-gp40 antibodies were variably present 12 months after FIV vaccination. The magnitude of the antibody response against both p24 and gp40 was significantly higher in the primary FIV vaccination group than in the annual FIV vaccination group. The differences in prime versus recall post-vaccinal antibody levels correlated with FIV PoC kit performance. Two FIV PoC kits that detect antibodies against gp40, namely Witness® and Anigen Rapid®, showed 100% specificity in cats recently administered an annual FIV vaccination, demonstrating that they can be used to accurately distinguish vaccination and infection in annually vaccinated cats. A third FIV PoC kit, SNAP® Combo, had 0% specificity in annually FIV-vaccinated cats, and should not be used in any cat with a possible history of FIV vaccination. This study outlines the antibody response to inactivated Fel-O-Vax® FIV whole-virus vaccine, and demonstrates how best to diagnose FIV infection in jurisdictions where FIV vaccination is practiced.

Metabolism of vitamin D in patients with primary biliary cirrhosis and alcoholic liver disease

1985 ◽  
Vol 69 (5) ◽  
pp. 561-570 ◽  
Author(s):  
E. Barbara Mawer ◽  
H. J. Klass ◽  
T. W. Warnes ◽  
Jacqueline L. Berry
Keyword(s):  
Vitamin D ◽  
Liver Disease ◽  
Primary Biliary Cirrhosis ◽  
Alcoholic Liver Disease ◽  
Vitamin D3 ◽  
Control Group ◽  
Biliary Cirrhosis ◽  
Vitamin D2 ◽  
Dihydroxyvitamin D3 ◽  
Poor Renal Function

1. The metabolism of isotopically labelled vitamin D2 and D3 has been investigated in eight patients with primary biliary cirrhosis and in five controls. The concentration of labelled vitamin D2 was lower than that of vitamin D3 in serum of patients with primary biliary cirrhosis on days 1 and 2 after intravenous injection (P < 0.005 and P < 0.05, respectively) but no difference was seen in controls. 2. Similar amounts of labelled 25-hydroxyvitamin D2 and D3 were seen in serum of the control group; the same pattern was observed in the primary biliary cirrhosis group, and no significant differences were observed between the two groups. 3. In both control and primary biliary cirrhosis groups, the serum concentration of labelled 24,25-dihydroxyvitamin D2 exceeded that of 24,25-dihydroxyvitamin D3 (significant for controls on day 2, P < 0.02) but concentrations in the two groups were not different. 4. Concentrations of labelled 25,26-dihydroxyvitamin D3 were significantly higher than those of 25,26-dihydroxyvitamin D2 in the primary biliary cirrhosis group at all times and in the control group on days 2 and 3. Both 25,26-dihydroxyvitamin D2 and D3 were higher in the serum of patients with primary biliary cirrhosis than in controls (significant on day 1, P < 0.05). 5. Urinary excretion over days 0–3 of radioactivity from both vitamins D2 and D3 was significantly higher in the primary biliary cirrhosis group than in controls: 12.03 vs 1.80% for vitamin D2 and 8.98 vs 1.76% for vitamin D3(P < 0.005). Vitamin D2-derived urinary radioactivity in primary biliary cirrhosis correlated strongly with serum bilirubin (P = 0.005). 6. The metabolism of labelled vitamin D3 was studied in seven patients with alcoholic liver disease, three of whom showed low serum concentrations of labelled 25-hydroxyvitamin D3 suggesting impaired hepatic synthesis. The 25-hydroxylation response was quantified as the relative index of 25-hydroxylation and was significantly related to two other indices of liver function. It is concluded that impaired 25-hydroxylation of vitamin D may occur in alcoholic liver disease and results from hepatocellular dysfunction. 7. Less than the predicted amounts of 1,25-dihydroxyvitamin D3 were produced in four of the seven patients with alcoholic liver disease; this defect may be attributable in part to decreased precursor 25-hydroxyvitamin D and to poor renal function.

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