Does a Low Level of Expression of HLA Molecules Engender Autoimmunity?

Raulet, David H.; Schillaci, Onofrio; Scopinaro, Francesco; Abramson, Lior; Retsas, Spyros; Krag, David N.; Moffat, Jr; Ashikaga, Tomoko; McMasters, K. M.; Edwards, Mark; Ross, Merrick I.

doi:10.1056/nejm199901283400413

Cited by 7 publications

(6 citation statements)

References 12 publications

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“…In these patients, the low level expression of HLA class I antigens on developing erythroid precursors may render them susceptible to KIR‐mediated lysis by auto‐reactive NK or cytotoxic T cells. This phenomenon was previously demonstrated in malignant melanoma cell lines, and is also thought to operate in PRCA (6–9).…”

supporting

confidence: 57%

A sustained response to low dose interferon‐α in a case of refractory pure red cell aplasia

Nadeau

Meyerson

Warren

et al. 2004

European J of Haematology

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Acquired pure red cell aplasia (PRCA) may be the result of a cellular or humoral autoimmune process. One proposed mechanism is the destruction of erythroid progenitors by self-reactive, cytotoxic T cells or natural killer (NK) cells. These cells normally express MHC class I receptors (KIR) which inhibit cytotoxicity when the target cell expresses the HLA class I antigen(s) they bind. Therefore, loss of these antigens on maturing erythroid progenitors may render them susceptible to destruction by the pathogenic cells. Interferon-alpha (INF-alpha) increases HLA class I expression on hematopoietic precursor cells. Therefore, we initiated a trial of INF-alpha in a patient with refractory PRCA. Following treatment, he developed transfusion independence, and a sustained normal hematocrit. Analysis of bone marrow erythroid cells revealed an increase in expression of HLA class I molecules. INF-alpha should be used in a controlled trial in patients with PRCA to determine its activity and mechanism of action.

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supporting

confidence: 57%

A sustained response to low dose interferon‐α in a case of refractory pure red cell aplasia

Nadeau

Meyerson

Warren

et al. 2004

European J of Haematology

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“…As MHC class I‐negative cells can be selectively recognized and destroyed by NK cells, 40,41 we investigated whether there are any NK cells infiltrating the MHC I‐negative anagen hair bulb in normal human skin. Examining CD56 and CD57 as frequently employed standard human NK cell markers, 37,38 no such indications were found, as intrafollicular CD56+ cells were detected only extremely rarely, and this only inside the distal, MHC I+ ORS, while no CD57+ cells at all were found in the hair follicle epithelium.…”

Section: Discussionmentioning

confidence: 99%

“…The almost complete MHC class I negativity of human DP cells in situ is in line with the MHC class I negativity reported for the DP of rat anagen hair follicles, 7 while it contrasts with the corresponding antigen expression patterns in mice: the DP is H-2b1 in murine anagen VI hair follicles. 1,4 As MHC class I-negative cells can be selectively recognized and destroyed by NK cells, 40,41 we investigated whether there are any NK cells infiltrating the MHC I-negative anagen hair bulb in normal human skin. Examining CD56 and CD57 as frequently employed standard human NK cell markers, 37,38 no such indications were found, as intrafollicular CD561 cells were detected only extremely rarely, and this only inside the distal, MHC I1 ORS, while no CD571 cells at all were found in the hair follicle epithelium.…”

Section: Discussionmentioning

confidence: 99%

The human hair follicle immune system: cellular composition and immune privilege

Christoph

Müller-Röver

Audring

et al. 2000

British Journal of Dermatology

326

335

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The immunology of the hair follicle, its relationship with the 'skin immune system' and its role in hair diseases remain biologically intriguing and clinically important. In this study, we analysed the immunoreactivity patterns of 15 immunodermatological markers to determine the cellular composition and immune privilege of the human hair follicle immune system in anagen VI (growth phase). The most prominent cells located in or around the hair follicle were Langerhans cells, CD4+ or CD8+ T cells, macrophages and mast cells, whereas B cells, natural killer cells and gammadelta T cells were found very rarely. Langerhans cells (CD1a+, major histocompatibility complex, MHC class II+), and T cells (CD4+ or CD8+) were predominantly distributed in the distal hair follicle epithelium, whereas macrophages (CD68+, MHC class II+) and mast cells (Giemsa+) were located in the perifollicular connective tissue sheath. Transmission electron microscopy confirmed low numbers of immune cells in the proximal hair follicle epithelium, and very few macrophages and Langerhans cells were seen in the dermal papilla. Melanophages were observed in the connective tissue sheath and dermal papilla. MHC class I (HLA-A, -B, -C) and beta2-microglobulin immunoreactivity was found on most skin cells, but was substantially reduced on isthmus keratinocytes and virtually absent in the proximal hair follicle epithelium. Apart from the absence of Fas ligand immunoreactivity, the sharply reduced numbers of T cells and Langerhans cells, and the virtual absence of MHC class I expression all suggest that the anagen proximal hair follicle constitutes an area of immune privilege within the hair follicle immune system, whose collapse may be crucial for the pathogenesis of alopecia areata.

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“…This observation has been interpreted as supportive for the importance of fetalematernal microchimerism in the etiology of autoimmune diseases (see below). Unusually low levels of HLA antigens have previously been associated with the occurrence of autoimmunity [21].…”

Section: Traditional Conceptsmentioning

confidence: 99%