Segregation study of the soluble 39 KD HLA class I heavy chain

Kubens, Britta S.; Päβler, M.; Grosse‐Wilde, H.

doi:10.1016/0198-8859(93)90163-u

Cited by 5 publications

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“…The lack of correlation of FHC levels with the E% of its size fractions in HBD can be explained with the previous findings, showing that the enhanced E% (> 50%) of BV detected in some healthy individuals is due to an alternative RNA splicing and inherited in association with HLA haplotypes (Kubens et al , 1994). On the other hand, the correlation of increased FHC with the E% of tFHC, together with the reduced E% (< 50%) of AV in 77% of MM patients as compared with that observed in only 35% of HBD, indicated that the FHC increase in MM was mostly a tFHC increase.…”

Section: Discussionsupporting

confidence: 55%

“…While AV release occurs through a shedding process, controversy still exists about the origin of BV. Initial studies in healthy individuals (Krangel, 1986; Haga et al , 1991) showed that its expression had no pathological significance, as it is produced following deletion of exon 5 (the one coding for the transmembrane region) based on an alternative RNA splicing and appears to be inherited in association with HLA haplotypes (Kubens et al , 1994). However, studies performed in vitro on solid and lymphoid tumour cell lines (Datema et al , 1999), and limited papain digestion experiments of detergent‐solubilized cellular or soluble HLA‐I have shown that, similarly to CV (Demaria et al , 1994), FHC with a size similar to that of BV can also be released by lytic cleavage at the cell surface, and membrane‐type metalloprotease (MT‐MPs) enzymes seem to be involved in this process (Datema et al , 1999).…”

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confidence: 99%

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Size variants of beta‐2‐microglobulin‐free human leucocyte antigen class I heavy chain make different contributions to its serum increase in multiple myeloma

et al. 2002

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Summary. We previously showed that serum beta -2-microglobulin (b2m)-free human leucocyte antigen (HLA) class I heavy chain (FHC) levels were increased in MM and correlate with disease activity. The present investigation, carried out in 124 multiple myeloma patients, studied the expression of the three size variants of FHC, namely the 42 kDa intact heavy chain (A variant, AV), released through a shedding process, and the truncated FHC (tFHC) 39 kDa (BV) and 36-35 kDa (CV) released by means of membrane-type metalloprotease activity. The increase in FHC correlated with a high expression percentage of BV (r ¼ 0AE32, P ¼ 0AE0002) and tFHC (r ¼ 0AE42, P < 0AE0001), which could help to discriminate multiple myeloma from monoclonal gammopathy of undetermined significance (tFHC mean ratio ¼ 3AE2; Mann-Whitney U-test, P < 0AE0001). tFHC levels highly correlated with other disease activity markers, namely haemoglobin (r ¼ )0AE35; Spearman's rank, P ¼ 0AE0001), percentage of bone marrow plasma cells (r ¼ 0AE4, P < 0AE0001) and b2m levels (r ¼ 0AE36, P < 0AE0001), while only the last barely correlated (r ¼ 0AE2, P ¼ 0AE03) with AV. Finally, the 0AE4, 0AE57 and 0AE71 mg/l BV, tFHC and (to a lesser extent) FHC cut-off values divided patients into two groups with different survival curves (P ¼ 0AE0005, P ¼ 0AE0025 and P ¼ 0AE04 respectively). These data are in favour of a correlation between disease aggressiveness and cleavage of these variants by membrane-type metalloprotease enzymes.Keywords: b2m-free HLA class I heavy chain, multiple myeloma, monoclonal gammopathy of undetermined significance, soluble HLA-I.Two forms of soluble human leucocyte antigen (HLA) class I can usually be found in sera: the beta-2-microglobulin (b2m)-associated HLA class I heavy chain (HLA-I) and b2m-free HLA class I heavy chain (FHC). FHC consists of three size variants, namely the intact lipid-soluble 43 kDa heavy chain (A variant, AV) and the two truncated forms, namely the water-soluble 39 kDa (B variant, BV), which lacks the transmembrane segment, and the 34-36 kDa (C variant, CV), which lacks the transmembrane and the intracytoplasmic portions of the molecule. While AV release occurs through a shedding process, controversy still exists about the origin of BV. Initial studies in healthy individuals (Krangel, 1986;Haga et al, 1991) showed that its expression had no pathological significance, as it is produced following deletion of exon 5 (the one coding for the transmembrane region) based on an alternative RNA splicing and appears to be inherited in association with HLA haplotypes (Kubens et al, 1994). However, studies performed in vitro on solid and lymphoid tumour cell lines (Datema et al, 1999), and limited papain digestion experiments of detergent-solubilized cellular or soluble HLA-I have shown that, similarly to CV (Demaria et al, 1994), FHC with a size similar to that of BV can also be released by lytic cleavage at the cell surface, and membrane-type metalloprotease (MT-MPs) enzymes seem to be involved in this process (Datema et al, 1999)...

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Section: Discussionsupporting

confidence: 55%

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confidence: 99%

Size variants of beta‐2‐microglobulin‐free human leucocyte antigen class I heavy chain make different contributions to its serum increase in multiple myeloma

et al. 2002

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“…Sodium dodecylsulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) and Western blotting were performed as described (24). Briefly, JEG3 cells (1×10 6 ) were solubilized in 100 μl lysis buffer (0.05% NP40, 0.05 M Tris‐HCl, 5 mM EDTA, pH 8.0) for 30 min at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Detection of soluble HLA‐G molecules in plasma and amniotic fluid

et al. 1999

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Although the cDNA sequence of HLA-G antigens is compatible with their expression as soluble molecules (sHLA-G), the determination of native sHLA-G levels in body fluids has not yet been described. The lack of this information is likely to reflect the difficulties in developing an assay suitable to measure sHLA-G antigens in the presence of soluble HLA-A, -B and -C (sHLA-I) antigens, since most of the available anti-HLA-G mAb do not detect soluble beta2-m associated HLA-G antigens or crossreact with sHLA-I antigens. Therefore, we have developed a two-step assay which eliminates the interference of classical HLA class I antigens. In the first step, the sample is depleted of sHLA-I antigens and of HLA-E antigens with mAb TP25.99. Then, HLA-G antigens are captured with mAb W6/32 and detected with anti-beta2-m mAb in ELISA. Utilizing this assay, sHLA-G antigen levels were measured in EDTA plasma from 92 controls with known HLA types, 28 women at delivery and the corresponding cord bloods and in 50 amniotic fluids. Mean sHLA-G plasma levels did not differ between males (24.9+/-3.0 SEM ng/ml; n=42) and females (20.1+/-2.1 SEM ng/ml; n = 50). However, sHLA-G levels in HLA-A11 positive probands (mean: 13.0+/-4.4 SEM ng/ml; n=12) were significantly (P<0.05) lower than in HLA-A11 negative ones (mean: 24.5+/-2.0 SEM ng/ml; n=80). sHLA-G levels in women at delivery (mean: 22.9+/-2.2 SEM ng/ml; n=28) were in the range of controls but were significantly (P<0.001) reduced in the corresponding cord bloods (mean: 13.8+/-1.5 SEM ng/ml; n=28). sHLA-G levels in amniotic fluids (mean: 15.5 + 1.0 SEM ng/ml; n=50) were significantly (P<0.001) lower than in plasma. sHLA-G levels were 5 and 11% of those of sHLA-I antigens in plasmas and amniotic fluids, respectively. Individual sHLA-G levels were not correlated with sHLA-I levels. SDS-PAGE analysis of plasma sHLA-G antigens revealed two molecular variants with a 35 kD and a 27 kD MW corresponding to the sizes of sHLA-G1 and -G2 isoforms. In conclusion, our study has shown that the two-step assay we have developed is reliable in measuring sHLA-G antigen levels. This assay will facilitate the analysis of the biological and clinical significance of sHLA-G antigens in plasma.

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“…The second polypeptide chain showed a molecular weight of 80 kDa that was reduced to 48 kDa after papain treatment . Kubens et al . could also detect two polypeptide chains but at 33 and 12 kDa, which were identified to correspond to the HLA‐I heavy chain and β 2‐microglobulin, respectively.…”

Section: Structure and Origin Of Smhc Moleculesmentioning

confidence: 99%

Soluble major histocompatibility complex molecules in immune regulation: highlighting class II antigens

Bakela

Athanassakis

2017

Immunology

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SummaryThe involvement of major histocompatibility complex (MHC) antigens in the development and regulation of immune response has been well defined over the years, starting from maturation, antigenic peptide loading, migration to the cell membrane for recognition by the T-cell receptor and recycling for immune response cessation. During this intracellular trafficking, MHC antigens find a way to be excreted by the cells, because they can be found as soluble MHC class I (sMHC-I) and class II (sMHC-II) molecules in all body fluids. Although secretion mechanisms have not been sufficiently studied, sMHC molecules have been shown to display important immunoregulatory properties. Their levels in the serum have been shown to be altered in a variety of diseases, including viral infections, inflammation, autoimmunities and cancer, etc. while they seem to be involved in a number of physiological reactions, including maintenance of tolerance, reproduction, as well as mate choice vis-a-vis species evolution. The present review aims to present the thus far existing literature on sMHC molecules and point out the importance of these molecules in the maintenance of immune homeostasis.

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Segregation study of the soluble 39 KD HLA class I heavy chain

Cited by 5 publications

References 0 publications

Size variants of beta‐2‐microglobulin‐free human leucocyte antigen class I heavy chain make different contributions to its serum increase in multiple myeloma

Size variants of beta‐2‐microglobulin‐free human leucocyte antigen class I heavy chain make different contributions to its serum increase in multiple myeloma

Detection of soluble HLA‐G molecules in plasma and amniotic fluid

Soluble major histocompatibility complex molecules in immune regulation: highlighting class II antigens

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