Disease relevance of IGKV1D-22

• The isolate was identified with use of Lim-Benyesh--Meinick enterovirus typing serum pools as coxsackievirus Type A-9 [1].
• A group of 15 patients with refractory Hodgkin's disease were treated in a phase I/II trial with the natural-killer (NK)-cell-activating bispecific monoclonal antibody HRS-3/A9, which is directed against the Fc gamma receptor III (CD16 antigen) and the Hodgkin's associated CD30 antigen [2].
• The 24 paired sera from EV4-infected subjects were also tested by immunoblot technique against three other enteroviruses: EV21, coxsackievirus A9 and poliovirus 1 [3].

High impact information on IGKV1D-22

• GCs increased constitutive levels of A8 and S100A9 (A9) mRNA in human monocytes [4].
• The synovial membrane of rheumatoid patients treated with high dose i.v. methylprednisolone contained higher numbers of A8/A9-positive macrophages than pre- or posttreatment samples [4].
• Expression of SLC26A7-A9 proteins in Xenopus oocytes demonstrated chloride, sulfate, and oxalate transport activity, suggesting that they encode functional anion exchangers [5].
• The SLC26A7-A9 proteins are structurally very similar at the amino acid level to the previous family members and show tissue-specific expression in kidney, testis, and lung, respectively [5].
• Here we present data that the S100A8/A9 protein complex represents the exclusive arachidonic acid-binding proteins in human neutrophils [6].

Biological context of IGKV1D-22

• In view of the unusual abundance in neutrophilic cytosol (approximately 40% of cytosolic protein) our findings assign an important role for S100A8/A9 as mediator between calcium signaling and arachidonic acid effects [6].
• The treatment was well tolerated and the maximum tolerated dose was not reached at 64 mg/m2, the highest dose given due to limited amounts of HRS-3/A9 available [7].
• DNA preparations from 150 randomly selected clones were labeled and annealed to XY and 4XY human DNA, and to DNA from a human-mouse hybrid cell line that had retained only the human X-chromosome (A9/HRBC2). cDNA clones sharing homology with DNA from the X chromosome annealed to A9/HRBC2-DNA and hybridized more intensely to 4XY DNA than to XY DNA [8].

Anatomical context of IGKV1D-22

• Stimulation of neutrophil-like HL-60 cells with phorbol 12-myristate 13-acetate led to the secretion of S100A8/A9 protein complex, which carried the released arachidonic acid [6].
• S100A8/A9 is present in the synovial fluid of patients with gout and arthritis and is secreted by activated monocytes; however, its mechanism of release by neutrophils remains unknown [9].
• Here, we show that S100A8/A9 is released by neutrophils stimulated with MSUM crystals and that this release could be enhanced by preincubating neutrophils with granulocyte macrophage-colony stimulating factor [9].
• RA inhibited the expression of S100A8/A9 and keratinocyte differentiation, which were induced by interleukin-1alpha [10].
• In the present study the MAb A9 (immunoglobulin G1 [IgG1]) was identified from hybridomas raised in BALB/c mice immunized with cell wall antigen of Aspergillus fumigatus [11].

Associations of IGKV1D-22 with chemical compounds

• When elevation of intracellular calcium level was induced by A23187, release of arachidonic acid occurred without secretion of S100A8/A9 [6].
• Monosodium urate monohydrate crystals induce the release of the proinflammatory protein S100A8/A9 from neutrophils [9].
• Neutrophil preincubation with the Src kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d]pyrimidine and the Syk tyrosine kinase inhibitor trans-3,3',4,5'-tetrahydrozystilbene significantly reduced the release of S100A8/A9, suggesting that the Src tyrosine kinase family and Syk were involved [9].
• A new haemoglobin variant: haemoglobin Anantharaj alpha 11 (A9) lysine replaced by glutamic acid [12].

Analytical, diagnostic and therapeutic context of IGKV1D-22

• The expression of S100A8/A9 mRNA and the production of calprotectin in normal human gingival keratinocytes were examined by northern blotting and enzyme-linked immunosorbent assay, respectively [10].
• Sequence analysis identified a Lys substituting for Gln substitution at position alpha-11 (A9) [13].

References