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LAD1  -  ladinin 1

Homo sapiens

Synonyms: LAD, LADA, Lad-1, Ladinin-1, Linear IgA disease antigen
 
 
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Disease relevance of LAD1

  • The nature and expression pattern of the 97 kDa linear IgA bullous dermatosis antigen (LAD-1) and its role in epidermolysis bullosa have not been fully elucidated [1].
  • LAD-1, the linear IgA bullous dermatosis autoantigen, is a novel 120-kDa anchoring filament protein synthesized by epidermal cells [2].
  • Cardiogenic shock occurred only in patients with LAD1 lesions, but apart from this the clinical presentation bore no consistent relation to the site of disease [3].
  • Because this protein appears to be involved in the process of dermal-epidermal cohesion, this study sought to determine the involvement of LAD-1 in the pathology of junctional epidermolysis bullosa (JEB) [4].
  • IgA antibodies from linear IgA disease sera react with antigens of 97 kDa (LABD97) and 120 kDa (LAD-1), both of which appear to be fragments of the extracellular domain of bullous pemphigoid 180 (type XVII collagen) [5].
 

Psychiatry related information on LAD1

  • Significant line differences were also found with the slip funnel test (AA > ANA for time in a sprawling posture; P > NP but HAD1 < LAD1 and HAD2 < LAD2 for time escaping), but the directions of line differences were not consistently related to those in alcohol drinking [6].
 

High impact information on LAD1

  • We describe a patient with clinical features compatible with a moderately severe phenotype of LAD-1 but who expresses the beta2 integrins lymphocyte function- associated molecule (LFA)-1 and Mac-1 at 40%-60% of normal levels [7].
  • Leukocyte adhesion deficiency 1 (LAD-1) is characterized by absent or dysfunctional beta2 integrin (CD18), leading to defective chemotaxis, adherence, phagocytosis, and bacterial killing [8].
  • Dysfunctional LAD-1 neutrophils and colitis [8].
  • The chronic colitis described in this article associated with the dysfunctional neutrophils of LAD-1 represents a distinct pathology from the commonly encountered forms of inflammatory bowel disease (IBD) [8].
  • A case of nonspecific colitis clinically resembling Crohn's disease in a patient with the severe form of LAD-1 (0.5% < CD18) has been previously reported [8].
 

Biological context of LAD1

  • Also associated with anchoring filaments is a novel protein, ladinin, which serves as autoantigen in the linear IgA disease, and the corresponding gene, LAD1, has been mapped to human chromosome 1 [9].
  • There is a significant diurnal rhythm of paw and tail latency in both of the alcohol preferring lines (iP5C and HAD1) but not in the nonpreferring lines (iNP1 and LAD1) [10].
  • This is the first mutation located in the intracellular domain of BPAG2, and resides 817 bp upstream from the N-terminal amino acid sequence of LAD-1 [1].
  • Dual BP180/LAD-1 reactivity with IgG and IgA was associated with a more severe phenotype [11].
 

Anatomical context of LAD1

  • A normal proteolytic processing event results in the shedding of the BP180 extracellular domain (LAD1) from the keratinocyte cell surface [12].
  • After the injection of papaverine in the midportion of the left anterior descending coronary artery (LAD), the diameter of the proximal LAD (LAD1) was measured by quantitative angiography, whereas that of the proximal circumflex artery (LCx) served as control segment [13].
  • Absence of the common beta chain (CD18) leads to leukocyte adhesion deficiency-1 (LAD1) in humans [14].
  • METHODS: Female HAD1 and LAD1 rats were surgically implanted with cannula into the lateral ventricle [15].
  • Linear IgA disease sera depleted of reactivity to NC16A by immunoadsorption continued to react with both the LAD-1 antigen and BP180 by immunoblotting and with the basement membrane zone by indirect immunofluorescence microscopy [5].
 

Associations of LAD1 with chemical compounds

  • Neutrophils isolated from a child with severe leukocyte adhesion deficiency 1 (LAD1) had a complete absence of expression of the CD11/CD18 beta2 integrin family of adhesion molecules, and were shown to be deficient in the in vitro adhesion and migration properties [16].
 

Other interactions of LAD1

 

Analytical, diagnostic and therapeutic context of LAD1

References

  1. The 97 kDa linear IgA bullous dermatosis antigen is not expressed in a patient with generalized atrophic benign epidermolysis bullosa with a novel homozygous G258X mutation in COL17A1. Shimizu, H., Takizawa, Y., Pulkkinen, L., Zone, J.J., Matsumoto, K., Saida, T., Uitto, J., Nishikawa, T. J. Invest. Dermatol. (1998) [Pubmed]
  2. LAD-1, the linear IgA bullous dermatosis autoantigen, is a novel 120-kDa anchoring filament protein synthesized by epidermal cells. Marinkovich, M.P., Taylor, T.B., Keene, D.R., Burgeson, R.E., Zone, J.J. J. Invest. Dermatol. (1996) [Pubmed]
  3. Isolated disease of left anterior descending coronary artery. Angiocardiographic and clinical study of 218 patients. Brooks, N., Cattell, M., Jennings, K., Balcon, R., Honey, M., Layton, C. British heart journal. (1982) [Pubmed]
  4. LAD-1 is absent in a subset of junctional epidermolysis bullosa patients. Marinkovich, M.P., Tran, H.H., Rao, S.K., Giudice, G.J., Balding, S., Jonkman, M.F., Pas, H.H., McGuire, J.S., Herron, G.S., Bruckner-Tuderman, L. J. Invest. Dermatol. (1997) [Pubmed]
  5. Autoantibodies in a subgroup of patients with linear IgA disease react with the NC16A domain of BP1801. Zillikens, D., Herzele, K., Georgi, M., Schmidt, E., Chimanovitch, I., Schumann, H., Mascaro, J.M., Diaz, L.A., Bruckner-Tuderman, L., Bröcker, E.B., Giudice, G.J. J. Invest. Dermatol. (1999) [Pubmed]
  6. Performance in the cross-maze and slip funnel tests of four pairs of rat lines selectively bred for divergent alcohol drinking behavior. Salimov, R.M., McBride, W.J., Sinclair, J.D., Lumeng, L., Li, T. Addiction biology. (1996) [Pubmed]
  7. A novel leukocyte adhesion deficiency caused by expressed but nonfunctional beta2 integrins Mac-1 and LFA-1. Hogg, N., Stewart, M.P., Scarth, S.L., Newton, R., Shaw, J.M., Law, S.K., Klein, N. J. Clin. Invest. (1999) [Pubmed]
  8. Dysfunctional LAD-1 neutrophils and colitis. Uzel, G., Kleiner, D.E., Kuhns, D.B., Holland, S.M. Gastroenterology (2001) [Pubmed]
  9. Molecular complexity of the cutaneous basement membrane zone. Uitto, J., Pulkkinen, L. Mol. Biol. Rep. (1996) [Pubmed]
  10. Pain thresholds in alcohol preferring and non-preferring rats: diurnal and repeated trial line differences. Kimpel, M.W., Brown, M.M., Froehlich, J.C. Alcohol. Clin. Exp. Res. (2003) [Pubmed]
  11. Bullous pemphigoid antigen II (BP180) and its soluble extracellular domains are major autoantigens in mucous membrane pemphigoid: the pathogenic relevance to HLA class II alleles and disease severity. Oyama, N., Setterfield, J.F., Powell, A.M., Sakuma-Oyama, Y., Albert, S., Bhogal, B.S., Vaughan, R.W., Kaneko, F., Challacombe, S.J., Black, M.M. Br. J. Dermatol. (2006) [Pubmed]
  12. BP180 (type XVII collagen) and its role in cutaneous biology and disease. Van den Bergh, F., Giudice, G.J. Advances in dermatology. (2003) [Pubmed]
  13. Loss of flow-dependent coronary artery dilatation in patients with hypertension. Antony, I., Lerebours, G., Nitenberg, A. Circulation (1995) [Pubmed]
  14. CD18 in Monogenic and Polygenic Inflammatory Processes of the Skin. Peters, T., Sindrilaru, A., Wang, H., Oreshkova, T., Renkl, A.C., Kess, D., Scharffetter-Kochanek, K. J. Invest. Dermatol. (2006) [Pubmed]
  15. Effects of neuropeptide Y on sucrose and ethanol intake and on anxiety-like behavior in high alcohol drinking (HAD) and low alcohol drinking (LAD) rats. Badia-Elder, N.E., Stewart, R.B., Powrozek, T.A., Murphy, J.M., Li, T.K. Alcohol. Clin. Exp. Res. (2003) [Pubmed]
  16. Migration of CD18-deficient neutrophils in vitro: evidence for a CD18-independent pathway induced by IL-8. Morland, C.M., Morland, B.J., Darbyshire, P.J., Stockley, R.A. Biochim. Biophys. Acta (2000) [Pubmed]
  17. 97 kDa linear IgA bullous dermatosis antigen localizes in the lamina lucida between the NC16A and carboxyl terminal domains of the 180 kDa bullous pemphigoid antigen. Ishiko, A., Shimizu, H., Masunaga, T., Yancey, K.B., Giudice, G.J., Zone, J.J., Nishikawa, T. J. Invest. Dermatol. (1998) [Pubmed]
  18. Type XVII collagen (BP180) and LAD-1 are present as separate trimeric complexes. Pas, H.H., Kloosterhuis, G.J., Nijenhuis, M., de Jong, M.C., van der Meer, J.B., Jonkman, M.F. J. Invest. Dermatol. (1999) [Pubmed]
  19. Localized bullous pemphigoid in a patient with B-cell lymphoma. Egan, C.A., Florell, S.R., Zone, J.J. South. Med. J. (1999) [Pubmed]
 
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