No Zinc Deficiency But a Putative Immunosuppressive Role for Labile Zn in Patients with Systemic Autoimmune Disease

Nossent, Jiri; Lester, Sue; Rischmueller, Maureen; Zalewski, Peter D.

doi:10.2174/1573397111666151026223501

Cited by 5 publications

(3 citation statements)

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“…Other studies reported similar results 47 , 48 . However, some studies did not observe a significant difference in serum Zn concentrations between SLE patients and healthy controls which is similar to the finding of the present study 49 , 50 .…”

Section: Discussionsupporting

confidence: 92%

Environmental risk factors of systemic lupus erythematosus: a case–control study

Refai

Hussein

Abdou

et al. 2023

Sci Rep

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Systemic lupus erythematosus (SLE) is a complicated chronic autoimmune disorder. Several genetic and environmental factors were suggested to be implicated in its pathogenesis. The main objective of this study was to examine how exposure to selected environmental factors was associated with SLE risk to support the development of disease preventive strategies. A case–control study was conducted at the Rheumatology outpatient clinic of Alexandria Main University Hospital, in Alexandria, Egypt. The study sample consisted of 29 female SLE patients, and 27 healthy female controls, who matched the cases on age and parity. Data were collected by a structured interviewing questionnaire. Blood levels of lead, cadmium, and zinc of all participants were assessed by flame atomic absorption spectrometry. The multivariate stepwise logistic regression model revealed that five factors showed significant association with SLE, namely living near agricultural areas, passive smoking, blood lead levels ≥ 0.075 mg/L, and exposure to sunlight (odds ratio (OR) 58.556, 95% confidence interval (CI) 1.897–1807.759, OR 24.116, 95% CI 1.763–329.799, OR 18.981, 95% CI 1.228–293.364, OR 9.549, 95% CI 1.299–70.224, respectively). Whereas walking or doing exercise were significantly protective factors (P = 0.006). The findings of this study add to the evidence that SLE can be environmentally induced. Preventive measures should be taken to address the environmental risk factors of SLE.

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Section: Discussionsupporting

confidence: 92%

Environmental risk factors of systemic lupus erythematosus: a case–control study

Refai

Hussein

Abdou

et al. 2023

Sci Rep

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“…This is especially important regarding autoimmune diseases, since a number of them are associated with disturbed zinc homeostasis, such as rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, and colitis [ 4 , 42 , 43 , 44 ]. Since T cell maturation, differentiation, and function is reliant on adequate zinc status [ 32 , 45 , 46 ], this connection is likely to be one reason for the development or progression of autoimmune diseases.…”

Section: Discussionmentioning

confidence: 99%

The Intracellular Free Zinc Level Is Vital for Treg Function and a Feasible Tool to Discriminate between Treg and Activated Th Cells

Maywald

Wang

Rink

2018

IJMS

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The intracellular free zinc level and zinc distribution are important for cellular function. Both are highly variable and are altered due to intrinsic zinc pool fluctuation via buffering and muffling reactions. Multiple autoimmune diseases are associated with pathologically changed zinc levels, which provoke altered signal transduction leading to changed immune responses, cell differentiation, and function. For instance, immunological tolerance can be impaired, causing autoimmune diseases because of a malfunction of regulatory T cells (Tregs). We investigated the intracellular free zinc concentration of resting and activated T helper (Th) cells and Tregs in an allogeneic graft versus host disease model using fluorescence-activated cell sorting (FACS) analysis and enlightened cell function under nontoxic zinc concentrations and zinc deficiency by detecting cytokine secretion via enzyme-linked immunosorbent assay (ELISA). We exhibited for the first time that Tregs could be explicitly discriminated from other Th cell subsets using significantly increased intracellular free zinc levels. Moreover, the intracellular free zinc level was essential in maintaining the Treg phenotype and function, since zinc deficiency favored the pro-inflammatory immune response. Therefore, we hypothesize that the intracellular free zinc level in Th cells is essential in guaranteeing proper cellular function and can be used to discriminate Tregs from other Th cell subsets.

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“…However, recently, contrary to the above evidence, Nossent et al showed that labile zinc levels are unexpectedly high in patients with autoimmune diseases and they also suggested that zinc may be probably causing an immunosuppressive effect in these patients. [58] Hence, the exact mechanism by which zinc acts as an immunomodulator remains unclear.…”

Section: Lichen Planus (Loe 1 B)mentioning

confidence: 99%

Immune-enhancing agents in autoimmune skin diseases – A review

Francis

Jose

2022

JSSTD

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Immunosuppressive drugs are the main stay of treatment for autoimmune dermatoses. The main disadvantage of these drugs is the increased susceptibility to life-threatening infections. Hence, in recent years, there has been an enthusiastic search for newer groups of drugs that can reduce this risk. Immune enhancing agents are considered as the key players of future. Immune enhancers function by activating various elements of the immune system and thereby amplifying the immune responses. They can be specific or non-specific in action. The main autoimmune dermatoses where the benefits of these drugs have so far been utilized include alopecia areata, vitiligo, psoriasis, lichen planus, and discoid lupus erythematosus. Immunostimulants are available in both topical and systemic forms. Topical immune- enhancing agents include contact sensitizers (diphenylcyclopropenone, dinitrochlorobenzene, and squaric acid dibutyl ester), anthralin, topical zinc, and interferons. Systemic agents include levamisole, zinc, probiotics, and so on. The exact mechanism of action of some of these drugs and other autoimmune conditions where they can be benefited is not completely understood. Another therapeutic agent that may come up in the future is individualized vaccines. Let us look forward to the days when individualized vaccines work wonders in the management of autoimmune diseases.

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No Zinc Deficiency But a Putative Immunosuppressive Role for Labile Zn in Patients with Systemic Autoimmune Disease

Abstract: There is no evidence of Zn deficiency in patients with pSS or SLE. Labile Zn levels are unexpectedly high in SLE patients, independent of cytokine levels and may play a role in immune modulation through increased NK numbers and autoantibody containment.

Cited by 5 publications

References 0 publications

Environmental risk factors of systemic lupus erythematosus: a case–control study

Environmental risk factors of systemic lupus erythematosus: a case–control study

The Intracellular Free Zinc Level Is Vital for Treg Function and a Feasible Tool to Discriminate between Treg and Activated Th Cells

Immune-enhancing agents in autoimmune skin diseases – A review

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