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Summary T lymphocyte hyperactivity and progressive inflammation in systemic lupus erythematosus (SLE) patients results in over‐expression of human leucocyte antigen (HLA)‐Ib on the surface of lymphocytes. These are shed into the circulation upon inflammation, and may augment production of antibodies promoting pathogenicity of the disease. The objective was to evaluate the association of HLA‐Ib (HLA‐E, HLA‐F and HLA‐G) antibodies to the disease activity of SLE. The immunoglobulin (Ig)G/IgM reactivity to HLA‐Ib and β2m in the sera of 69 German, 29 Mexican female SLE patients and 17 German female controls was measured by multiplex Luminex®‐based flow cytometry. The values were expressed as mean florescence intensity (MFI). Only the German SLE cohort was analysed in relation to the clinical disease activity. In the controls, anti‐HLA‐G IgG predominated over other HLA‐Ib antibodies, whereas SLE patients had a preponderance of anti‐HLA‐F IgG over the other HLA‐Ib antibodies. The disease activity index, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)‐2000, was reflected only in the levels of anti‐HLA‐F IgG. Anti‐HLA‐F IgG with MFI level of 500–1999 was associated with active SLE, whereas inactive SLE revealed higher MFI (>2000). When anti‐HLA‐F IgG were cross‐reactive with other HLA‐Ib alleles, their reactivity was reflected in the levels of anti‐HLA‐E and ‐G IgG. The prevalence of HLA‐F‐monospecific antibodies in SLE patients was also associated with the clinical disease activity. Anti‐HLA‐F IgG is possibly involved in the clearance of HLA‐F shed from lymphocytes and inflamed tissues to lessen the disease's severity, and thus emerges as a beneficial immune biomarker. Therefore, anti‐HLA‐Ib IgG should be considered as a biomarker in standard SLE diagnostics.

Some of the cytological and histochemical characteristics of hemocytes of Thyropygus poseidon were studied. Jone's system of classification of hemocytes was extended to millipede hemocytes. Seven classes were identified as prohemocytes, plasmatocytes, granular hemocytes, cytocytes, oenocytoids, spherule cells and adipohemocytes. Oenocytoids were rarely found. All cells except prohemocytes and oenocytoids sequestered oxidized products of catechol. Results of the histochemical tests for proteins also suggest that these cells sequester plasma proteins. Cytocytes do not bring about any visible coagulation similar to the hemocytes of some hemipteran insects. Granular hemocytes contain phenol‐oxidase capable of oxidising tyrosine as well as catechol, similar to the hemocytes of crustaceans. In this respect millipede hemocytes differ from insect hemocytes. It is suggested that these cell types may represent distinct cell lines and may not represent transformation of one cell type to another.

The number and the binding affinity, measured as the mean fluorescent intensity (MFI) of HLA-specific IgG antibodies, formed in the sera of end-stage organ disease patients and allograft recipients, referred to as sensitization, may restrict the availability of a donor organ and/or lead to graft failure after transplantation. The MFI of HLA Abs in sera is monitored with the Luminex-based single-antigen bead (SAB) immunoassay. The following two factors may impact the reliable measurement of MFI: one, the HLA structural variants on the SAB, namely, trimeric HLA (closed conformers, CC) and monomeric heavy chains (open conformers, OC); and two, the nature of the detection Abs, namely, IgG heavy-chain binding polyclonal-Fab (IgHPolyFab) or Fc-binding monoclonal-IgG (FcMonoIgG). Anti-CC Abs correlate with positive flow cross-matches, and are considered to be pathogenic and damaging to the graft, whereas anti-OC Abs appear to have little relevance to graft attrition. The presence of both CC and OC on beads may impair the reliability of monitoring the nature and MFI of pathogenic Abs. Our objective is to compare the MFI of the HLA Abs in the sera of 20 sensitized patients in two different SAB assays, with the two detection Abs. Our data reveal that the admixture of OC with CC on beads will affect the reliability of the measurement of the pathogenic Abs, and that FcMonoIgG is the more sensitive and specific detection Ab for the accurate assessment of HLA sensitization.

Blood loss after trauma induces several systemic inflammatory responses culminating in the dysfunction and failure of organs. In this issue of the British Journal of Nutrition, Relja et al. (1) have examined the inflammatory signals at the subcellular, cellular and tissue levels after haemorrhage-induced hepatic injury and resuscitation in rats. Hepatic injury and resuscitation induced the expression of intercellular adhesion molecule-1, neutrophil infiltration and necrosis in the liver, and augmented serum alanine transaminase and IL-6 levels. It also induced IkBa phosphorylation and the activation of NF-kB. Pre-treatment with green tea extract (GTE: catechins . 80 %, with .40 % of epigallocatechin gallate (EGCG)) suppressed the inflammatory responses at all levels, including neutrophil infiltration, intercellular adhesion molecule-1 expression and the release of IL-6, and, importantly, suppressed the activation of NF-kB.The inflammatory responses occurring in the liver after haemorrhage are parallel to the inflammatory events occurring after inducing ischaemia, and EGCG is also active in the latter setting (2 -5) . The anti-inflammatory efficacy of EGCG demonstrated in all these studies generates a unifying hypothesis. Hepatic injury induced by ischaemia (2) caused oxidative stress with enhanced production of reactive oxygen species and TNF-a; both mediated the expression of nuclear factors and kinases, activating the signal transduction pathways to trigger cell death. The liver that stained positive for NF-kB in the ischaemia group remained negative in the EGCG-pretreated group. Neutrophil infiltration that was enhanced in the ischaemia group was significantly reduced after EGCG. Ischaemia-induced myocardial injury (3) also caused significant neutrophil infiltration, an increase in plasma IL-6, and activation of IkB kinase and NF-kB in the tissues. EGCG pre-treatment significantly reduced myocardial damage, neutrophil infiltration and plasma IL-6, and also suppressed the NF-kB pathway. Intestinal injury induced by ischaemia (4) also resulted in an enhanced production of reactive oxygen species, neutrophil infiltration and activation of NF-kB. EGCG pre-treatment significantly deactivated NF-kB, decreased neutrophil infiltration and lowered reactive oxygen species production. All these studies support the conclusion derived by Relja et al. and collectively point out that induced inflammatory responses are mediated through NF-kB-dependent mechanisms, and EGCG per se or in combination with other catechins suppresses NF-kB activation and alleviates inflammation.There are enumerable reports on the efficacy of EGCG per se or EGCG in combination with other catechins (epigallocatechin or epicatechin gallate or gallocatechin gallate) (5 -9) on inflammatory responses induced by different exogenous and endogenous factors. The inflammatory inducers include polymicrobial sepsis (10) , lipopolysaccharide (5 -7,11) , Staphylococcus aureus enterotoxin B (12) , Helicobacter pylori infection (13) , IL-1b alone (8,14 -16) ...

A monoclonal antibody (mAb) binds to an antigen recognizing an epitope (a sequence of amino acids). A protein antigen may carry amino acid sequence unique to that antigen as well as sequences found in other proteins. Human leukocyte antigens (HLA), a family of proteins expressed by the Major Histocompatibility Complex gene family represent a special case, in that it displays a high degree of polymorphism. Every HLA molecule possesses both specific (private) epitopes and epitopes shared (public) with other HLA class Ia and class Ib molecules. HLA-E is overexpressed in cancer cells more than any other HLA Class I molecules. Therefore specific localization of HLA-E with mAbs is pivotal for developing targeted therapy against cancer. However, the commercially available mAbs for immunodiagnosis are polyreactive. We have developed anti-HLA-E mAbs and distinguished monospecific from polyreactive mAbs using Luminex multiplex single antigen bead (SAB) assay. HLA-E-binding of monospecific-mAbs was also inhibited by E-restricted epitopes. The amino acid sequences in the region of the epitopes bind to CD94/NKG2A receptors on CD8+ T cells and NK cells and block their antitumor functions. Monospecific-HLA-E mAbs recognizing the epitopes sequences can interfere with the binding to restore the anti-tumor efficacy of NK cells. Also, monospecific-mAbs augment the proliferation of CD4-/CD+ cytotoxic T-lymphocytes. Therefore, anti-HLA-E monospecific-mAb can serve as a double-edged sword for eliminating tumor cells.

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