DETECTION OF AUTOANTIBODIES AND ALLOANTIBODIES AGAINST PLATELET-ASSOCIATED ANIGENS

1987 ◽  
Author(s):  
R McMillan ◽  
P Tani ◽  
P Berchtold ◽  
F Millard
Keyword(s):  
Hla Antigens ◽  
Class I ◽  
High Dose ◽  
Hla Antibodies ◽  
Negative Results ◽  
Single Donor ◽  
Prognostic Group ◽  
Successful Outcomes ◽  
Well Assay ◽  
High Degree

Although autoantibodies against the platelet glycoproteins (GP) and a 1loantibodies toward class I HLA antigens have been demonstrated using various methods, practical techniques for their detection have not been available.We studied 59 patients with chronic immune thrombocytopenic purpura (ITP) where platelet-associated and plasma autoantibodies against the GP Ilb/IIIa complex and GP lb were measured using a newly developed imraunobead assay and a previously described microtiter well assay. The specificity of both assays depends on the monoclonal antibody employed (e.g., GPIIb/IIIa, lb or HLA). Platelet-associated autoantibody was detected using the immunobead assay in 21 of 28 patients (13 with anti-GPIIb/IIIa and 8 with anti-GPIb). Plasma autoantibodies were noted in 34 of 59 patients (21 with anti-GPIIb/IIIa, 11 with anti-GPIb and 2 with both). Positive results were noted in 30 of 59 ITP patients using the immunobead assay and in only 14 of 59 using the microtiter well assay, suggesting that solubilization prior to antibody addition, as in the microtiter well assay, alters epitope stability. However, the microtiter well assay appears to define a poor prognostic group. Of 11 patients with positive well assays who underwent splenectomy, only one achieved a complete remission, 3 have died and all require continuous high-dose steroids or immunosuppressants. Of the 31 thrombocytopenic controls studied, all gave negative results using both assays.The immunobead assay was adapted to specifically measure anti-HLA antibodies and was used to evaluate 51 single donor platelet transfusions given to 7 patients refractory to random platelets. Twenty-nine of 33 (88%) transfusions associated with a negative assay had successful outcomes (1 hr increment >7500) while only 2 of 18 (11.1%) episodes associated with a positive test had successful outcomes. Only 1 unsuccessful transfusion episode was associated with a negative immunobead and a positive antiglobulin test suggesting that transfusion-related alloantibodies, other than to class I HLA antigens, are an uncommon cause of refractoriness.We conclude that these two clinically adaptable assays are capable of measuring both autoantibodies and anti-HLA alloantibodies with a high degree of sensitivity.

scholarly journals A specific assay for anti-HLA antibodies: application to platelet donor selection

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1495-1499 ◽  
Author(s):  
FE Millard ◽  
P Tani ◽  
R McMillan
Keyword(s):  
Hla Antigens ◽  
Class I ◽  
Successful Outcome ◽  
Transfusion Therapy ◽  
Hla Antibodies ◽  
Vitro Assay ◽  
Single Donor ◽  
Platelet Survival ◽  
Successful Outcomes

Abstract Alloimmunization to donor class I HLA antigens represents a major obstacle to successful platelet transfusion therapy. It is desirable to distinguish alloimmunization from nonimmunologic causes of poor platelet survival to assess the need for HLA-matched, single-donor platelets. We describe a new in vitro assay for anti-HLA antibodies and report its application to the problem of platelet crossmatching. In contrast to previously described crossmatch techniques, the immunobead assay is specific for anti-HLA antibodies. The assay was used to evaluate 51 single-donor platelet transfusions given to seven patients from 35 different donors. Recipient plasma was assayed for antibodies directed against HLA antigens present on donor platelets. A one-hour posttransfusion corrected count increment of greater than or equal to 7,500 was considered a successful outcome. Twenty-nine of 33 (87.9%) transfusion episodes associated with a negative immunobead assay had successful outcomes. The four unsuccessful transfusions were associated with potential nonimmunologic causes of poor platelet survival. Only two of 18 (11.1%) episodes associated with a positive assay had successful outcomes. Only one unsuccessful transfusion episode was associated with a negative immunobead assay and a positive radiolabeled antiglobulin test result, which suggested that isolated alloantibodies to antigens other than class I HLA antigens are not a common cause of platelet refractoriness. Platelets stored in suspension at 4 degrees C or frozen in liquid nitrogen were found suitable for crossmatch testing.

scholarly journals A specific assay for anti-HLA antibodies: application to platelet donor selection

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1495-1499
Author(s):  
FE Millard ◽  
P Tani ◽  
R McMillan
Keyword(s):  
Hla Antigens ◽  
Class I ◽  
Successful Outcome ◽  
Transfusion Therapy ◽  
Hla Antibodies ◽  
Vitro Assay ◽  
Single Donor ◽  
Platelet Survival ◽  
Successful Outcomes

Alloimmunization to donor class I HLA antigens represents a major obstacle to successful platelet transfusion therapy. It is desirable to distinguish alloimmunization from nonimmunologic causes of poor platelet survival to assess the need for HLA-matched, single-donor platelets. We describe a new in vitro assay for anti-HLA antibodies and report its application to the problem of platelet crossmatching. In contrast to previously described crossmatch techniques, the immunobead assay is specific for anti-HLA antibodies. The assay was used to evaluate 51 single-donor platelet transfusions given to seven patients from 35 different donors. Recipient plasma was assayed for antibodies directed against HLA antigens present on donor platelets. A one-hour posttransfusion corrected count increment of greater than or equal to 7,500 was considered a successful outcome. Twenty-nine of 33 (87.9%) transfusion episodes associated with a negative immunobead assay had successful outcomes. The four unsuccessful transfusions were associated with potential nonimmunologic causes of poor platelet survival. Only two of 18 (11.1%) episodes associated with a positive assay had successful outcomes. Only one unsuccessful transfusion episode was associated with a negative immunobead assay and a positive radiolabeled antiglobulin test result, which suggested that isolated alloantibodies to antigens other than class I HLA antigens are not a common cause of platelet refractoriness. Platelets stored in suspension at 4 degrees C or frozen in liquid nitrogen were found suitable for crossmatch testing.

Prevalence and Significance of Pre-Formed Anti-HLA Antibodies in Hematopoietic Stem Cell Transplant Recipients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1174-1174
Author(s):  
Darshan Gautam Gandhi ◽  
Jennifer Holter ◽  
Mohamad Khawandanah ◽  
Robert B. Epstein ◽  
Julie Stoner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Graft Failure ◽  
Hla Antigens ◽  
Class Ii ◽  
Class I ◽  
Hla Antibodies ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Antibody Levels

Abstract Abstract 1174 Poster Board I-196 Introduction: The presence of sensitization to HLA antigens has been an important consideration in solid organ transplantation. It is considered a standard process to check for donor-specific allogeneic (allo) antibodies (DSA) and monitor formation of such antibodies post-transplant which could predict early and late graft failure. Most of the current data regarding the importance of anti-HLA (human leukocyte antigen) antibodies is available from renal transplant where presence of HLA antibodies is clearly associated with an increased risk of early graft loss up to the magnitude of 21%. It is routine to perform desensitization to alleviate these antibodies in an effort to enhance their chances of engraftment. The role of and approach to prior sensitization in the hematopoietic stem cell transplantation (HSC) setting is far less clear. This is of unique importance as a wider range of donor cell sources and transplant applications are utilized to treat hematologic diseases. Many of our patients have had multiple transfusions in the past, been pregnant or have had prior HLA mismatched allograft, all of which predispose to development of anti-HLA antibodies. Here we analyze the prevalence of Class I and Class II antibodies as a primary goal and also see if they correlate with graft survival. Methods: 52 patients were followed between July 2008 and July 2009 with hematologic malignancies including leukemia's, lymphoma's, multiple myeloma and others. 37/52 underwent transplantation of which 14 were unrelated donor (URD), 5 cord blood (CB) and 8 sibling (sib) transplants. Donors with corresponding HLA were excluded. Post-transplantation with day 100 antibody testing was performed in eligible patients. Antibody determination was done by testing the patients' sera with a panel of fluorescent beads coated with single HLA antigens using a solid-phase Luminex™ platform. Cut-point of 1500 [mean fluorescence intensity (MFI) ≥ 1500 defined as positive] was used for performing statistical analyses. The prevalence of positive antibody levels was compared among the transplant groups using a Fisher's exact test. Level of expression of antibodies was evaluated with MFI <500 considered negative, 500-1500 weak, 1500-3000 intermediate and >3000 strong. High resolution HLA typing was performed. Results: Class I antibodies were positive in 24 out of 52 total (46%) with 95% CI: 32% to 61%.14/37 (38%) who underwent transplantation (95% CI: 22% to 55%), 12/27 (44%) undergoing allo transplant, CB (20%), sib (38%), and URD (57%) were positive. The prevalence did not differ significantly among the transplant groups (p=0.3). Class II antibodies were positive in 8 out of 52 total (15%) with 95% CI: 7% to 28%. 5/37 (14%) who underwent transplantation (95% CI: 5% to 29%), 4/27 (15%) undergoing allo transplant, Sib (0%), CB (20%) and URD (21%) were positive. The prevalence did not differ significantly among the transplant groups (p=0.6). In females, 18/28 (64%) were positive for Class I or Class II antibodies of which 5/6 (83%) underwent URD transplants. Persistent antibody levels were detected in 3 of 4 patients tested at day 100 post transplant. Conclusions: Based on this limited pilot study we conclude that there is a high prevalence of anti-HLA antibodies present in recipients at the time of HSC transplantation. However detection of such antibodies did not jeopardize engraftment from various donor sources when HLA donor specific reactions are excluded. Bray et al showed higher incidence of graft failure associated with DSA. Takanashi et al showed that in CB transplants, antibodies were not significant unless the corresponding HLA was present in the CB unit. Based on these studies, we excluded donors with corresponding HLA. All but one patient, in whom donor specific anti-HLA antibodies were identified, achieved sustained marrow engraftment. The long term implications of antibody evolution and specificity to sustained marrow engraftment, graft vs. host and graft vs. tumor effects remain to be clarified. A larger prospective study will need to be conducted to definitely evaluate these relationships including our own which is currently under way. Disclosures: No relevant conflicts of interest to declare.

Class I HLA-Specific Antibodies Can Cause “false-positive” Test Results in the Serotonin Release Assay for Heparin-Induced Thrombocytopenia (HIT).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3506-3506
Author(s):  
Shiu-Ki Hui Rocky ◽  
Thomas M Ellis ◽  
Richard H. Aster ◽  
Brian R. Curtis
Keyword(s):  
Low Dose ◽  
Serotonin Release ◽  
Class I ◽  
High Dose ◽  
True Positive ◽  
Test Results ◽  
Hla Antibodies ◽  
Heparin Induced Thrombocytopenia ◽  
Dose Heparin ◽  
Release Assay

Abstract Abstract 3506 Poster Board III-443 A diagnosis of heparin-induced thrombocytopenia (HIT) is confirmed with support from the laboratory. Antibodies associated with HIT are specific for complexes made up of heparin and platelet factor 4 (PF4) and can be detected in a solid phase ELISA (PF4 ELISA). However, a functional test, the serotonin release assay (SRA) is regarded by many to be the “gold standard” for laboratory investigation of this disorder. In our facility, the SRA is performed by incubating serotonin-labeled platelets (pooled from three different group O donors) with test serum and low dose (0.1 units/ml) or high dose (100 units/ml) heparin and determining the percentage of total serotonin released. Release of serotonin (20-100%) with low dose heparin and inhibition of this release with high dose heparin is considered to be “positive” for platelet-activating HIT antibodies. Sera from some patients cause serotonin release with low dose heparin that is not inhibited with high dose heparin. The significance for these “indeterminate” reactions is unclear, but they are considered not to reflect the presence of “true” HIT antibodies. We studied selected serum samples from 238 patients referred for HIT testing. Of these, 119 tested “true” positive and 117 produced “indeterminate” reactions in the SRA. The same samples were tested for the presence of antibodies reactive with beads coated with various Class I HLA antigens using a flow cytometric bead assay (Flow PRA, One Lambda). Sera producing at least 30% release in SRA and reactive with at least 20% of the bead panel were selected for analysis. As shown in Figure 1, there was a high correlation between the likelihood of an “indeterminate” SRA test result and the presence of Class I HLA antibodies (p &lt;&lt; 0.0001). Figure 1 SRA Category No. with PRA &gt;/=20% No. with PRA &lt;20% Total Sample SRA “Indeterminate” (&gt;/=30% Release and Uninhibited by High Dose Heparin) 91 19 110 SRA “True Positive” (&gt;/=30% Release and Inhibited by High Dose Heparin) 36 72 108 As expected, there was a significant correlation between the strength of reactions produced by individual “true positive” sera in the SRA (% release) and in the PF4/heparin ELISA (O.D. value). However, in analyzing 38 sera with “true positive” test results in the SRA, we identified two that were negative in the PF4 ELISA and contained broad Class I HLA reactivity (reactive with 100% and 41% of the panel, respectively). We conclude 1) Class I HLA antibodies are the major cause of “indeterminate” reactions in the serotonin release assay and 2) A subset of these antibodies can be inhibited by high dose heparin and therefore mimics the behavior of “true” HIT antibodies in the SRA. Unless the PF4 ELISA test is used together with the SRA, this type of reaction could lead to an erroneous diagnosis of HIT. Disclosures: No relevant conflicts of interest to declare.

The Influence Of Anti-HLA Antibodies On Engraftment and Donor’s Chimerism Following Allogeneic Hematopoietic Stem Cell Transplantation From HLA-Mismatched Unrelated Donors

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4542-4542
Author(s):  
Miroslaw Markiewicz ◽  
Anna Koclega ◽  
Sylwia Mizia ◽  
Urszula Siekiera ◽  
Alicja Dobrowolska ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Graft Failure ◽  
Hla Antigens ◽  
Class I ◽  
Hla Antibodies ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Unrelated Donors

Introduction Although anti-HLA Antibodies (Abs) are considered an important factor of graft failure in solid organ transplants, their role in allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still undiscovered. Large polymorphism and immunogenicity of HLA-antigens and heterogeneity of anti-HLA Abs warrant the need of such investigation. The purpose of this study was to define the presence of anti-HLA Abs before allo-HSCT from HLA-mismatched unrelated donors and their impact on engraftment and post-transplant full donor’s chimerism. Material and Methods 70 HLA-mismatched donor/recipient pairs entered the study. Indication for allo-HSCT was: ALL, AML, CML, SAA, PNH, MDS and CLL. Preparative regimen was myeloablative in 68pts (97%) and reduced in 2pts (2.3%). Standard GVHD prophylaxis consisted of cyclosporine, methotrexate and pre-transplant anti-thymocyte globulin (69pts) or Alemtuzumab (1pt). HLA A,B,C,DR,DQ alleles were PCR-typed. Single HLA-antigen was mismatched in 46pts, single HLA-allele in 16pts, double antigens or alleles in 2 pts and another 2 pts had combined antigenic/allelic HLA mismatch. Anti-HLA A,B,C,DR,DQ,DP Abs were identified in sera collected prior to the conditioning treatment with use of automated DynaChip assay utilizing microchips bearing purified class I and class II HLA antigens. Post-transplant chimerism was analyzed using STR-PCR method at 30, 100-days and 1-year after allo-HSCT. Results Anti-HLA Abs pre-formed before allo-HSCT were detected in 32pts: against class I, II or both in 13(18.6%), 7(10%) and 12(17.1%) pts. Anti-HLA Abs were detected after allo-HSCT in 49pts: against class I, II or both in 22(32.4%), 7(10.3%) and 20(29.4%) pts, respectively. Anti-HLA Abs directed against the mismatched HLA antigens were observed in 4 pts before allo-HSCT. Although no Abs specific to mismatched HLA alleles were detected, Abs belonging to the same Cross-Reactive Groups (CREGs) were present in 5pts. No graft failure has been observed (graft failure was defined as absence of neutrophil recovery by day 30 after allo-HSCT or loss of donor’s chimerism). The detection of anti-HLA Abs before allo-HSCT was associated with decrease of post-transplant donor’s chimerism (18/31 vs 11/35, p=0.03). Anti-HLA Abs had no significant impact on engraftment of platelets and neutrophils. The median time to neutrophils engraftment was 16.9 days (range 7-31 days) in pts with and 18.9 days (range 13-30 days) in pts without anti-HLA Abs (p=0.188). The median time to platelets engraftment was 16.9 days (range 9-31 days) in patients with and 18.3 days (range 10-32 days) in pts without anti-HLA Abs (p=0.274). Conclusions Our preliminary results indicate, that anti-HLA Abs are present before transplantation in mismatched allo-HSCT recipients. They influence the post-transplant full donor’s chimerism, but they did not influence engraftment and graft failure. Disclosures: No relevant conflicts of interest to declare.

An EIA method on single donor solubilized HLA antigens for the identification of anti-HLA antibodies

1997 ◽  
Vol 19 (2) ◽  
pp. 129-136 ◽  
Author(s):  
M.-P. EMONDS ◽  
H. CLAEYS ◽  
A. VOLCKAERTS ◽  
J. DENDIEVEL ◽  
C. VERMYLEN
Keyword(s):  
Hla Antigens ◽  
Hla Antibodies ◽  
Single Donor

scholarly journals Biological and structural characterization of murine TRALI antibody reveals increased Fc-mediated complement activation

2020 ◽  
Vol 4 (16) ◽  
pp. 3875-3885
Author(s):  
Eveline A. N. Zeeuw van der Laan ◽  
Saskia van der Velden ◽  
Arthur E. H. Bentlage ◽  
Mads D. Larsen ◽  
Thijs L. J. van Osch ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Mhc Class I ◽  
Complement Activation ◽  
Structural Features ◽  
Cross Reactivity ◽  
Class I ◽  
High Dose ◽  
Binding Affinities ◽  
Hla Antibodies

Abstract Transfusion-related acute lung injury (TRALI) remains a leading cause of transfusion-related deaths. In most cases, anti-leukocyte antibodies in the transfusion product trigger TRALI, but not all anti-leukocyte antibodies cause TRALI. It has been shown that the anti–major histocompatibility complex (MHC) class I antibody 34-1-2S (anti–H-2Kd) causes TRALI in BALB/c mice (MHC class I haplotype H-2Kd), whereas SF1.1.10 (anti–H-2Kd) does not. In C57BL/6 mice (MHC class I haplotype H-2Kb), TRALI only occurs when anti-MHC class I antibody AF6-88.5.5.3 (anti–H-2Kb) is administered together with a high dose of 34-1-2S. It remains unknown which specific antibody characteristics are responsible for eliciting TRALI. We therefore investigated several biological and structural features of 34-1-2S compared with other anti-MHC class I antibodies, which on their own do not cause TRALI: SF1.1.10 and AF6-88.5.5.3. No substantial differences were observed between the TRALI-causing 34-1-2S and the TRALI-resistant SF1.1.10 regarding binding affinity to H-2Kd. Regarding binding affinity to H-2Kb, only AF6-88.5.5.3 potently bound to H-2Kb, whereas 34-1-2S exhibited weak but significant cross-reactivity. Furthermore, the binding affinity to FcγRs as well as the Fc glycan composition seemed to be similar for all antibodies. Similar Fc glycosylation profiles were also observed for human TRALI-causing donor anti-HLA antibodies compared with human anti-HLA antibodies from control donors. 34-1-2S, however, displayed superior complement activation capacity, which was fully Fc dependent and not significantly dependent on Fc glycosylation. We conclude that TRALI induction is not correlated with Fab- and Fc-binding affinities for antigen and FcγRs, respectively, nor with the composition of Fc glycans; but increased Fc-mediated complement activation is correlated with TRALI induction.

Monitoring for HLA Antibodies in Cord Blood Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2031-2031
Author(s):  
Jonathan A. Gutman ◽  
Susan K. McKinney ◽  
Sandra L. Warnock ◽  
Anajane Smith ◽  
Ann E. Woolfrey ◽  
...  
Keyword(s):  
Cord Blood ◽  
Graft Rejection ◽  
Cord Blood Transplantation ◽  
Hla Antigens ◽  
Class Ii ◽  
Class I ◽  
Antibody Specificity ◽  
Hla Antigen ◽  
Hla Antibodies ◽  
Blood Transplantation

Abstract Though graft rejection in hematopoietic cell transplantation (HCT) is presumed to be mediated primarily by host anti-donor T cells and natural killer cells, host antibodies which generate antibody dependent cellular cytotoxic reactions to donor antigens may also contribute. For patients undergoing HCT with a cord blood graft which is usually markedly mismatched to the recipient, alloimmunization is a potential significant issue. Cross-matching is not able to be performed secondary to limited cell numbers available from a cord blood graft. Delayed hematopoietic recovery and graft failure are known complications of cord blood transplantation (CBT), and though likely related primarily to small graft size and presence of primarily naïve immune cells in a cord blood graft, HLA antibodies may also contribute. At our center, we investigate recipient alloimmunity in all patients undergoing CBT to guide donor selection. Patients are first screened for the presence of antibodies against HLA antigens using an ELISA-based assay in which patient serum is tested against pools of purified class I and class II HLA antigens bound in wells of a plastic microtiter plate. Serum from patients noted to have evidence of HLA antibodies prompts further testing to identify the specific HLA antibodies using panels of color coded plastic microspheres each coated with a single purified class I or class II HLA antigen. To date, 4 of 29 patients screened have had evidence of HLA alloimmunization. Further investigation of antibody specificity in one patient undergoing double unit CBT demonstrated antibodies to HLA-Bw6, an epitope known to be present on one of the donor units. Because no other donors were available, the unit was used. Following a reduced intensity preparative regimen (RIT), the patient engrafted neutrophils on day 24 and platelets on day 42. However, the HLA-Bw6 positive unit was absent on all chimerism studies (beginning day 21 post transplantation). Three other patients with HLA alloimmunization did not have identifiable antibody specificity directed against mismatched HLA antigens, and engrafted neutrophils on days 25, 29, 25 and platelets on days 29, 41, and 102 respectively. To our knowledge, we are the first to report monitoring for alloimmunization in CBT and the first to describe the outcome of grafting a cord blood unit known to be HLA antibody incompatible with the patient. When patients undergo double unit CBT, cells from both units can generally be detected in the blood of the recipient during the first month, especially following RIT conditioning, but one unit eventually and consistently prevails (though predictive factors for the winning unit have not yet been satisfactorily described). In this case the compatible unit prevailed and there was no evidence at day 21 of cells from the antibody incompatible unit. Although we cannot attribute cause and effect to the anti-Bw6 alloantibody, it is interesting to note that all seven other patients transplanted on the same RIT protocol have demonstrated at least minimal bone marrow contributions to chimerism from both units at day 28. Hence, alloimmunization may be an important factor influencing graft rejection in CBT. CBT patients should likely be screened for HLA antibodies, and positive screenings warrant further investigation to avoid whenever possible donor/recipient mismatches against which the patient is sensitized. Ongoing monitoring will help clarify the clinical significance of this issue.

Anti-HLA Antibodies in Allogeneic Hematopoietic Stem Cell Transplantation From HLA-Mismatched Unrelated Donors

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4475-4475
Author(s):  
Anna Koclega ◽  
Miroslaw Markiewicz ◽  
Urszula Siekiera ◽  
Alicja Dobrowolska ◽  
Sylwia Mizia ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hla Antigens ◽  
Class I ◽  
Hla Antibodies ◽  
Hematopoietic Stem ◽  
Unrelated Donors

Abstract Abstract 4475 Introduction: Anti-HLA Antibodies (Abs) are considered an important factor in solid organ transplants and transfusion medicine, but role of humoral arm of immunological response to HLA antigens in allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unknown. Large polymorphism and immunogenicity of HLA-antigens and heterogeneity of anti-HLA Abs warrant the need of such investigation. The purpose of this study was to define presence and profiles of anti-HLA Abs detected before or after allo-HSCT from HLA-mismatched unrelated donors and their impact on allo-HSCT results. Material and methods: 35 HLA-mismatched donor/recipient pairs entered the study. Indication for allo-HSCT was: ALL (7pts), AML(18pts), CML(5pts), SAA(2pts), CLL(1pt), MDS(1pt) and PNH (1pt). Preparative regimen was myeloablative in 33pts (94.3%) and reduced in 2pts (5.7%). Standard GVHD prophylaxis consisted of cyclosporine, methotrexate and pre-transplant anti-thymocyte globulin (34pts) or Alemtuzumab (1pt). HLA A, B, C, DR, DQ alleles were PCR-typed. 21(60%) pts had mismatch of single HLA-antigen: A-4(11.4%), B-1(2.8%), C-13(37%), DQ-3(8,5%); 10(28.5%) pts had mismatch of single HLA-allele: A-3(8.5%), B(11.4%), DQ-3(8.5%); 4 pts had double antigenic (A+C and A+DQ) or combined antigenic/allelic (A/B and C/A) HLA mismatches. Anti-HLA A, B, C, DR, DQ, DP Abs were identified in sera collected before start of the conditioning treatment and +30 days, +100 days and 1 year after allo-HSCT with use of automated DynaChip assay utilizing microchips bearing purified class I and class II HLA antigens. Results: Anti-HLA Abs pre-formed before allo-HSCT were detected in 17(48.5%) pts: against class I, II or both in 6(35%), 4(24%) and 7(41%) pts. Anti-HLA Abs were detected after allo-HSCT in 25(71.4%) pts, against class I, II or both in 9(36%), 3(12%) and 13(52%) pts, respectively. In 7 pts anti-HLA Abs were not detected neither before nor after allo-HSCT. Anti-HLA Abs directed against the mismatched HLA antigens were observed in 4 pts before and in 10 pts after allo-HSCT, no anti-HLA Abs specific against mismatched alleles were detected. Allo-HSCT results obtained in studied subgroups are presented in the Table below: Conclusions: Our preliminary results indicate that anti-HLA Abs are present pre- or post-transplant in mismatched allo-HSCT recipients and may be potentially responsible for the occurrence of complications, what needs to be further investigated and analyzed. Disclosures: No relevant conflicts of interest to declare.

929 Not Another Abscess - A Case of Streptococcal Myositis Misdiagnosed as a Right Axillary Abscess

2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
O Oyende ◽  
J Jackman
Keyword(s):  
White Cell Count ◽  
General Surgeon ◽  
High Dose ◽  
General Anaesthetic ◽  
Microbiological Analysis ◽  
Reactive Protein ◽  
Affected Tissue ◽  
Life Threatening ◽  
History Of ◽  
High Degree

Abstract Introduction Streptococcal myositis is a rare form of infectious myositis caused by Lansfield A beta-haemolytic streptococci. It is characterised by rapidly spreading inflammation that can result in severe systemic toxicity and necrosis of the affected tissue if not diagnosed and aggressively treated. Presentation We report a case of a 42-year-old male who presented with a one-week history of worsening right axillary swelling that progressed to painful swelling of his arm. Inflammatory markers were significantly elevated with a white cell count of 17 ×109/L and C-reactive protein of 212 mg/L. On examination, a fluctuant axillary swelling was appreciated, and a decision was made for incision and drainage under general anaesthetic. Intraoperative aspiration of his arm revealed copious purulent fluid prompting intraoperative orthopaedic consult and exploration of the anterior compartment in which there was extensive involvement of the biceps muscle. The microbiological analysis revealed gram-positive cocci in chains, and microbiology advice sought for tailoring of antibiotic regimen. He has recovered well. Discussion Though uncommon, the emergency general surgeon should have a high degree of suspicion when evaluating soft tissue infections to avert potentially disastrous outcomes. Conclusion Early diagnosis, aggressive management with high-dose intravenous antibiotics, and surgical debridement are principles to treat this rare, life-threatening infection.

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