HLA Phenotype Positive

The purpose of study was determination of HLA -antigens I and II classes as predictors of ineffectiveness of initial steroid therapy, and according prognozonegative markers of chronic glomerulonephritis with nephrotic syndrome. Methods. In 59 chronic glomerulonephritis with nephrotic syndrome patients (steroid sensitive n=33 (1 gr.) and steroid resistant’s n= 26 (2 gr.)) and 350 healthy donors( control group) studied HLA antigens I and II classes of the special anti- HLA-antigens panel (20 antigens of locus A, 31 – of locus B and 9- of locus DR). Result. In patients with chronic glomerulonephritis, nephrotic syndrome with hormone sensitivity relative risk is high at the presents of A28 (RR=8,5, r р <0,001), it made attributive risk (=0,37). In comparison with a control group, RR>2 for antigens A11 (RR=2,23), A23 (RR=4,28), A24 (RR=3,3), A29 (RR=10,78) that A30 (RR=11,23); attributive risk more than 0,1 for the antigen A11 (=0,16) ; A24 (=0,13), other did not differ from control. Subzero connection is exposed for the antigens of A2 (р<0,001), А9 (р=0,007). In locus antigen B14 (RR=5,65, р =0,001) are exposed, B44 (RR=48,25, р =0,004), B51(RR=12,32, р =0,006) and attributive risk of development of disease (according =0,24, 0,12 ; 0,14); and antigens B38 and B41 (RR=11,57, р=0,05). The steroid sensitivity was associated with the antigens B5 (p=0,033), B12 (p=0,005) and B35 (p=0,021). In locus DR made etiologic faction antigens DR4 (RR=7,0 and =0,24) DRw52 (RR=7,0 and =0,25). Conclusions. For patients with chronic glomerulonephritis with a nephrotic syndrome antigens of HLA-B14,B38, B51, DRw52 are associated with steroid sensitivity. The attributive risk of steroid resistance is high for split A19+31+32, antigens B8, B55.

Download Full-text

HLA phenotype and systemic sclerosis-rheumatoid arthritis overlap syndrome: Comment on the article by Horiki et al

Arthritis & Rheumatism ◽

10.1002/1529-0131(199804)41:4<757::aid-art36>3.0.co;2-8 ◽

1998 ◽

Vol 41 (4) ◽

pp. 757-758 ◽

Cited By ~ 1

Author(s):

Shin'ichiro Yasunaga ◽

Masanori Higuchi ◽

Hiroaki Nishizaka ◽

Shigeru Yoshizawa ◽

Takahiko Horiuchi

Keyword(s):

Rheumatoid Arthritis ◽

Systemic Sclerosis ◽

Overlap Syndrome ◽

Hla Phenotype

Download Full-text

HLA-phenotype and hemochromatosis in Germany

Gastroenterology ◽

10.1016/0016-5085(78)90913-7 ◽

1978 ◽

Vol 75 (3) ◽

pp. 555-556 ◽

Cited By ~ 4

Author(s):

Herbert Dyrszka ◽

Gerd Eberhardt ◽

Günter Eckert

Keyword(s):

Hla Phenotype

Download Full-text

Idiopathic Hemochromatosis and Iron Overload in Alcoholic Liver Disease: Differentiation by HLA Phenotype

Gastroenterology ◽

10.1016/s0016-5085(19)31760-3 ◽

1977 ◽

Vol 73 (4) ◽

pp. 655-658 ◽

Cited By ~ 61

Author(s):

Marcel Simon ◽

Michel Bourel ◽

Bernard Genetet ◽

Renée Fauchet ◽

Gilles Edan ◽

...

Keyword(s):

Liver Disease ◽

Iron Overload ◽

Alcoholic Liver Disease ◽

Hla Phenotype ◽

Idiopathic Hemochromatosis

Download Full-text

De-Immunization of Human Factor VIII: Identification of Epitopes in the C2 Domain

Blood ◽

10.1182/blood.v112.11.1030.1030 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1030-1030

Author(s):

Leonard Moise ◽

Jonathan Skupsky ◽

Ryan Tassone ◽

Julie A McMurry ◽

William D Martin ◽

...

Keyword(s):

T Cell ◽

C2 Domain ◽

Protein Antigens ◽

Peptide Epitopes ◽

Hla Dr ◽

Human Factor Viii ◽

Hla Phenotype ◽

Hla Binding ◽

Partial Activity

Abstract Most immune responses to protein antigens are dependent on T-cell recognition of discrete peptide epitopes presented in an MHC groove. The pattern of peptide recognition can be predicted from the primary structure of a given protein based on residues that bind (anchor) to a given HLA phenotype. Algorithms such as EpiMatrix can be applied to identify such epitopes and measure the potential immunogenicity of proteins based on epitope content. One approach to reduce immunogenicity is to generate recombinant proteins whose constituent epitopes have been modified so as to reduce their HLA binding. Modification of the sequence can be performed in silico using algorithms such as OptiMatrix. This “de-immunization” method has been used effectively with a number of therapeutic proteins already in use in clinical trials. It may therefore also be possible to target those residues of fVIII that, while contributing to HLA binding, can be mutated without altering the functional ability of fVIII to initiate clotting. We have begun this de-immunization process with the fVIII, starting with C2 domain because C2 has been confirmed to be a major target of both T cells and inhibitory antibodies. Using EpiMatrix, we selected 10 peptides in human fVIII that would be predicted to bind to eight class II HLA DR molecules that encompass over 95% of the U.S. population. These epitopes were synthesized and eight of the ten were assayed in vitro and found to bind to HLA at IC50 <100μM. Immunization of fVIII knockout mice with whole fVIII or with constituent fVIII peptide epitopes resulted in significant T cell proliferation to the peptide epitopes as measured by thymidine incorporation assays. By contrast, homologous peptide epitopes modified by 1–2 residues elicited significantly lower levels of proliferation. These preliminary results point to the feasibility of generating a de-immunized fVIII molecule with reduced immunogenicity; validation of these results is planned. If such proteins retain even partial activity to initiate clotting, then they would become useful in treating hemophilia A patients to avoid inhibitor formation. (Supported by NIH R43 HL088834-01)

Download Full-text