Lack of NK cells in lupus patients with renal involvement

Abstract

We have previously shown that patients with SLE have significantly lower percentages and absolute numbers of NK(CD3-/CD16+56) cells in their peripheral blood compared with normals. Patients with active disease had very low levels of NK cells and the reduction was also associated with patients who had renal involvement. We have now performed a serial study immunophenotyping 11 patients with SLE and renal involvement using dual colour immunofluorescence and flow cytometry. Patients were tested every three months on an average of three occasions. As a control, nine SLE patients without renal involvement were immunophenotyped for similar intervals; 11 normal controls were also tested. Major lymphocyte subsets (T, B and NK) remained very stable during serial bleeds. However, the NK cell populations were decreased significantly in patients with renal involvement both as percentages (5 +/- 6 vs 9 +/- 5, P < 0.0001) and absolute counts (75 +/- 108 vs 109 +/- 52, P < 0.001) in comparison to non-renal patients. Analysis of disease activity using BILAG score showed an inverse correlation between renal system activity and percentage and absolute number of NK cells (P < 0.002 and 0.01, respectively). In this study we have also analysed a CD8 T cell subset which we have not studied before. We have found a significantly increased percentage of CD38+CD8+ T cells(activated CD8 subset) in patients with SLE in comparison to normal controls. We did not find any association with the CD38+CD8+ T cells and disease activity as measured by BILAG or renal involvement. NK cells are important factors in immunity against virus infections and tumour cells. CD38+CD8+T cells are increased in viral infections. We speculate that the lack of NK cells in SLE patients might have an association with increased CD38 expression.

Down-regulation of natural killer cells and of g/d T cells in systemic lupus erythematosus. Does it correlate to autoimmunity and to laboratory indices of disease activity?

“…9,28 Several authors have underlined how a`normal' non-MHC-restricted cytotoxic activity, both of NK cells and of T lymphocytes, is important in preventing autoimmune processes. 1,18,29 An alteration of this component of the immune response seems to be important in the development of SLE since NK cells are decreased signi®cantly in active disease states and in patients with renal involvement. 17,18 A signi®cantly lower frequency of gad T cells, that are known to belong mainly to the cytotoxic subset, 6 has also been found in PBMCs of SLE patients as compared to normal subjects, although no correlation has been reported with either clinical or laboratory indices of disease activity.…”

“…19 A decreased number of NK cells seems, in fact, to play an important role in the course and prognosis of SLE and to re¯ect increased disease activity and renal involvement. 17,18 Few con¯icting data exist concerning the possible involvement of TCR gad positive lymphocytes, able to mediate a cytotoxic function similar to that of the NK cells. 13 No signi®cant correlation has indeed been found, so far, in SLE, among this T cell subset and other clinical or laboratory measurements of disease activity.…”

Natural killer cells: In health and disease

“…58 However, in systemic lupus erythematosus (SLE), patients show a variable and moderate reduction of NK-cell numbers along with reduced CD4 + CD25 + Treg cells. 59,60 The function of NK cells is downregulated in these patients and there is a shift from the CD56 dim population to the CD56 bright subset. 61,62 It is also indicated that NK cells in these patients have a reduced cytotoxic effect.…”

The Genetics of Systemic Lupus Erythematosus

“…Located within the 4p15 region is the gene encoding lymphocyte differentiation antigen CD38 (ADP ribosyl cyclase/cyclic ADPribose hydrolase), formerly known as OKT10. Several studies have shown increased levels of CD38 expressing T and B cells in SLE patients compared to the controls [108][109][110][111]. Studies of mice deficient in CD38 show alterations of the humoral immune responses [112].…”