The identification of a novel HLA-B*35:279 allele in a Czech patient is described. This allele is identical to the B*35:03:01 variant except the G/A nucleotide exchange at position 652 of the HLA-B gene that corresponds to the amino acid substitution from valine to isoleucine in alpha 3 domain of the HLA-B antigen.
- MeSH
- alely * MeSH
- HLA-B antigeny genetika imunologie izolace a purifikace MeSH
- lidé MeSH
- sekvence nukleotidů MeSH
- substituce aminokyselin MeSH
- testování histokompatibility MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Terapeutický efekt nepříbuzenské transplantace krvetvorných buněk (TKB) je nejvíce určován genetickou – HLA – neshodou mezi příjemcem a dárcem. Ta umožňuje jak u malignit žádoucí reakci štěpu proti leukemii (GVL – graft versus leukemia effect) snižující riziko relapsu, tak reakci štěpu proti hostiteli (GVHD-graft versus host disease) zvyšující mortalitu. Práce se snaží shrnout současný pohled na celkový význam HLA shody a interpretovat kvalitativní a kvantitativní efekt neshod v individuálních HLA genech na výsledek TKB od dospělého nepříbuzného dárce a to především u maligních onemocnění. Standardem je v současnosti snaha nalézt dárce alelicky shodného minimálně v HLA-A,-B,-C a–DRB1, protože izolovaná neshoda v každém z těchto genů zvyšuje mortalitu o přibližně 10 % a vícečetné neshody mají dokonce synergický negativní vliv. Efekt neshody je však významně ovlivněn stadiem základního onemocnění, protože u vysoce rizikových nemocných je v důsledku akcentované GVL reakce mnohem méně významný či dokonce zanedbatelný. S možnou výjimkou HLA-C lokusu u transplantace periferními krvetvornými buňkami jsou neshody na alelické i antigenní úrovni zřejmě srovnatelně tolerované. Je-li nutné akceptovat neshodného dárce, pak u kostní dřeně je lépe vyhnout se neshodám v HLA-A či DRB1, u periferních krvetvorných buněk je nejhůře tolerovanou „antigenní“ neshoda v HLA-C. Mimo HLA shodu existuje celá řada faktorů na straně dárce, které ovlivňují výsledek TKB a zde nutno zdůraznit především včasnost provedení transplantace, protože rychlost nalezení nepříbuzného dárce a neprodlené provedení TKB je takřka stejně důležité jako stupeň shody.
The therapeutic effect of unrelated donor stem cell transplantation (SCT) is predominantly determined by genetic non-identity – HLA-mismatch – between recipient and donor. This facilitates both the desirable graft versus leukaemia (GVL) effect, which reduces the risk of relapse in malignancies as well as the graft-versus-host disease (GVHD), which increases mortality. This paper attempts to summarize the current view on the overall significance of HLA match and to interpret the qualitative and quantitative effect of mismatches in individual HLA genes on the outcome of SCT from an unrelated adult donor, particularly in malignant diseases. The current standard involves an effort to find an allele-level matched donor at least in HLA-A,-B,-C,-DRB1, because isolated mismatch in each of these genes increases mortality by approximately 10% and multiple mismatches actually have a negative synergistic effect. However, the consequences of incompatibility are significantly influenced by disease stage, as in high-risk patients these are much less significant or even negligible because of the accentuated GVL response. With the possible exception of the HLA-C locus, mismatches either on allelic or antigenic level seem to be comparably tolerated in peripheral blood stem cell transplantation. If it is necessary to accept a mismatched donor, then in the case of bone marrow it is best to avoid mismatches in HLA-A and DRB1, while in the case of peripheral blood stem cells the worst tolerated “antigenic” mismatch involves HLA-C. Apart from HLA match, there are many factors on the donor side that affect SCT outcome. These especially include timely transplantation, as the speed of finding an unrelated donor and SCT within the shortest possible time are almost as important as the degree of HLA-compatibility.
- Klíčová slova
- krvetvorné buňky,
- MeSH
- časové faktory MeSH
- dárci krve MeSH
- dospělí MeSH
- HLA antigeny genetika imunologie MeSH
- HLA-A antigeny genetika imunologie MeSH
- HLA-B antigeny genetika imunologie MeSH
- HLA-C antigeny genetika imunologie MeSH
- HLA-DRB1 řetězec genetika imunologie MeSH
- homologní transplantace MeSH
- krevní a lymfatické nemoci terapie MeSH
- lidé MeSH
- nepříbuzný dárce * MeSH
- reakce štěpu proti hostiteli genetika imunologie MeSH
- reakce štěpu proti leukémii imunologie MeSH
- rizikové faktory MeSH
- testování histokompatibility * metody MeSH
- transplantace kmenových buněk * MeSH
- výběr dárců MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- přehledy MeSH
AIMS: To determine the impact of HLA compatibility measured by the Compatibility Index, on survival, rate of rejections, malignancies and infections in patients after heart transplantation (HTx). METHODS: We carried out a retrospective analysis of 182 consecutive patients who underwent heart transplantation in our center from January 2001 to April 2010. According to degree of HLA-A, B and DR matching (Compatibility Index, CI) the patients were divided in two groups, Group A (n=83) with an IC 0-17 and group B (n=99) with an IC 18-26. There was no significant difference in demographic parameters between recipients and donors. RESULTS: We found no difference in rates of rejections or infections between Group A and Group B (AR: 22 (26.5%) vs. 34 (34.3%), P=0.2539; infections: 21 (25.3%) vs. 27 (27%) P=0.7637). The distribution of infections in terms of type (bacterial, viral, fungal, including Aspergillus) was similar in both groups. The incidence of malignant tumours was infrequent (3 (3.6%) vs. 4 (4.0%), P=0.8817). We found trend toward lower level of tacrolimus in Group A. Long term survival was similar in both groups. CONCLUSIONS: Based on the results of our single-center trial, we found no impact of higher degree of HLA-A,-B, and -DR matching on survival, rejection episodes or infection. Further large studies are necessary to confirm our hypothesis that subjects with better HLA compatibility could require lower dose immunosuppression.
- MeSH
- biologické markery metabolismus MeSH
- dospělí MeSH
- HLA antigeny imunologie MeSH
- HLA-A antigeny imunologie MeSH
- HLA-B antigeny imunologie MeSH
- HLA-DR antigeny imunologie MeSH
- hodnocení rizik MeSH
- imunosupresiva terapeutické užití MeSH
- Kaplanův-Meierův odhad MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- přežívání štěpu imunologie MeSH
- rejekce štěpu imunologie MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- senioři MeSH
- testování histokompatibility * metody MeSH
- transplantace srdce * metody mortalita MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Different strategies appear to improve the success in treatment of antibody-mediated rejection (AMR), although no one best method has yet emerged. The objective of this study was to compare the efficacy of the combination of Plasmapheresis/intravenous immunoglobulin (IVIg)/anti-CD20-based regimes versus high-dose IVIg alone in the treatment of AMR. Group A (12 patients) was treated with high-dose IVIg between January 2000 and December 2003; group B (12 patients) was treated by Plasmapheresis/IVIg/anti-CD20 between January 2004 and December 2005. Graft survival at 36 months was 91.7% in group B versus 50% in group A (p = 0.02). Donor-specific human leukocyte antigens (DSA) levels detected by Luminex single antigen (Luminex SA) and ELISA, 3 months postrejection are significantly lower in group B than in group A: DSA ELISA class 2 score 6-8 (p = 0.02), DSA mean intensity of fluorescence (MFI) max (p = 0.009) and DSA mean MFI (p = 0.0004). The persistence of elevated DSA levels posttreatment is more frequent in patients with graft loss as compared to those with preserved renal function: score 6-8 on ELISA (p = 0.04); mean MFI (p = 0.00009) and MFImax (p = 0.018). We conclude that: (1) high dose IVIg alone is inferior to Plasmapheresis/IVIg/anti-CD20 as therapy for AMR and (2)DSA postrejection can be quantified using solid phase assays, showing that 3 months after AMR, DSA levels are higher in patients with graft loss.
- MeSH
- antigeny CD20 imunologie MeSH
- B-lymfocyty imunologie MeSH
- biopsie MeSH
- dospělí MeSH
- fokálně segmentální glomeruloskleróza chirurgie MeSH
- HLA antigeny imunologie MeSH
- HLA-A antigeny imunologie MeSH
- HLA-B antigeny imunologie MeSH
- intravenózní imunoglobuliny terapeutické užití MeSH
- isoprotilátky imunologie krev MeSH
- kombinovaná terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- plazmaferéza MeSH
- rejekce štěpu imunologie patologie prevence a kontrola MeSH
- T-lymfocyty imunologie MeSH
- testování histokompatibility MeSH
- transplantace ledvin imunologie MeSH
- tvorba protilátek MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
BACKGROUND: Renal cell carcinomas have developed various strategies to escape immune cell recognition, including down-regulation or loss of classic HLA class I antigens (A, B, C) and aberrant expression of non-classic HLA class I antigens (G, E). In this study both classic and non-classic HLA class I antigens were tested in tumor specimens and established primary cell cultures derived from renal cell carcinoma patients. MATERIAL/METHODS: HLA class I antigens were evaluated by immunohistochemical staining and the intensity of cytoplasmic staining was measured semiquantitatively. Renal tumor tissue obtained from nephrectomy was used for the explant culture. MTT assay was performed to test the chemoresistance of primary cell line cultures to common cytostatics. RESULTS: HLA-G and HLA-E were found in 62% and 100% of the analyzed tumor samples, respectively. Markedly higher levels of the non-classic HLA-G and -E antigens compared with the classic HLA-A, -B, and -C antigens were observed. The cells of the control renal tissues were HLA-A, -B, -C, and -E positive and HLA-G negative. Cell line cultures were successfully established in 85% of the renal cell carcinoma specimens. No or minimal changes in classic HLA-A, B, and C antigen staining were observed during cultivation of the primary cell line cultures. No correlation between HLA class I antigen expression and chemoresistance, histopathological stage, or nuclear grade was found. CONCLUSIONS: These findings suggest that primary cell line cultures derived from surgical specimens of renal cell carcinomas are a feasible model for immunotherapy research through their high cultivation potential.
- MeSH
- buněčné kultury metody MeSH
- dospělí MeSH
- histokompatibilita - antigeny třídy I metabolismus MeSH
- HLA antigeny metabolismus MeSH
- HLA-A antigeny metabolismus MeSH
- HLA-B antigeny imunologie MeSH
- HLA-C antigeny MeSH
- HLA-G antigeny MeSH
- imunohistochemie MeSH
- imunoterapie MeSH
- karcinom z renálních buněk imunologie terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové buňky kultivované MeSH
- nádory ledvin imunologie terapie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
A novel HLA-B (human leukocyte antigen-B) allele, HLA-B*4442, was identified both in a Czech patient with leukaemia and in his mother. The presence of a novel allele was initially suspected because conflicting results were obtained by serological and DNA typing techniques. The HLA typing using the polymerase chain reaction-sequence-specific primers (PCR-SSP) at the two-digit level indicated an allele belonging to the HLA-B*44 group, whereas serological typing indicated HLA-B21. Typing with PCR-sequence-specific oligonucleotides (PCR-SSO) resulted in a unique reaction pattern that could not be assigned to a known allele, PCR-SSP typing at the four-digit level did not match any known B*44 allele, either. The sequencing-based typing of the HLA-B locus then revealed the novel B*4442 allele that is identical with B*4405 except a single C-->G nucleotide exchange at position 572. This exchange results in an amino acid substitution from serine to tryptophan at position 167 of the expressed HLA-B protein. The B21 serological reactivity of the novel B*4442 allele product was confirmed by employing an additional serological panel of typing sera. Our findings support previous reports claiming that serine at the position 167 in the alpha-2 domain of the HLA-B protein is a major determinant of the HLA-B44(12) serological epitope.
- MeSH
- alely MeSH
- bodová mutace imunologie MeSH
- financování organizované MeSH
- HLA-B antigeny genetika imunologie MeSH
- leukemie genetika imunologie MeSH
- lidé MeSH
- molekulární sekvence - údaje MeSH
- regulace genové exprese u leukemie genetika imunologie MeSH
- rodokmen MeSH
- sekvence nukleotidů MeSH
- substituce aminokyselin účinky léků MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Geografické názvy
- Česká republika MeSH
- MeSH
- hemolýza etiologie MeSH
- HLA-A2 antigen imunologie škodlivé účinky MeSH
- HLA-B antigeny imunologie škodlivé účinky MeSH
- krevní transfuze MeSH
- lidé MeSH
- potransfuzní reakce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- kazuistiky MeSH
- kongresy MeSH
- MeSH
- HLA-A antigeny imunologie MeSH
- HLA-B antigeny imunologie MeSH
- HLA-DQ antigeny imunologie MeSH
- HLA-DR antigeny imunologie MeSH
- lidé MeSH
- nekompatibilita krevních skupin imunologie MeSH
- transplantace heterologní imunologie MeSH
- transplantace kostní dřeně imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- abstrakty MeSH
