See the published version of this article at Arthritis Research & Therapy.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement and SLE disease activity
Erwei Sun
Department of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5664-513X
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Arthritis Research & Therapy.
Background: Necroptosis is a form of regulated necrosis that is involved in various autoimmune diseases. Mixed lineage kinase domain-like pseudokinase (MLKL) has been identified as a key executor of necroptosis, however, the significance of MLKL in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) has not been investigated. In this study, we aimed to determine the mRNA level of MLKL in PBMCs and examine its relationship with clinical features and serological parameters in SLE.
Methods: Real-time transcription-polymerase chain reaction analysis (RT-PCR) was used to determine expression of MLKL mRNA in PBMCs from 59 patients with SLE, 25 patients with rheumatoid arthritis (RA) and 30 age- and sex-matched healthy controls(HC). Spearman's correlation test was performed to assess the correlation of MLKL mRNA with clinical variables. The receiver operating characteristic curve (ROC) was created to evaluate the diagnostic value.
Results: Our results showed MLKL mRNA in PBMCs was upregulated in SLE patients compared to that in RA and HC individuals. SLE patients positive for anti-nuclear antibodies had significantly higher MLKL mRNA than antibody-negative patients. In SLE patients, MLKL mRNA was found to be upregulated in patients with lupus nephritis (LN) as compared with patients without LN, and also higher in active patients than in stable patients. MLKL mRNA level was significantly and positively correlated with c-reaction protein (CRP) (r=0.3577, p=0.0237), erythrocyte sedimentation rate (ESR) (r=0.4091, p=0.0043), serum immunoglobulin G (IgG) concentration (r=0.3546, p=0.0289) and the numbers of positive antinuclear antibodies (ANAs) (r=0.3945, p=0.0432). ROC analysis showed that MLKL mRNA in PBMCs had an area under the curve of 0.9277 (95% CI 0.8779 - 0.9775, p<0.001) to discriminate SLE from controls.
Conclusions: These results suggest that increased MLKL mRNA level in the PBMCs of SLE patients is correlated with renal involvement and disease activity, identifying a subgroup of patients with SLE or LN who may benefit from early diagnosis and therapies targeting MLKL.
Keywords
SLE, necroptosis, MLKL, mRNA, PBMCs, diagnosis
Figure 1
Figure 2
Figure 3
Figure 4
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 22 Sep, 2020
Published
On 14 Oct, 2020
No community comments so far
Editorial decision: Accept
On 23 Sep, 2020
Review #1 received
Received 22 Sep, 2020
Reviewer #1 agreed
On 18 Sep, 2020
Editor assigned
On 17 Sep, 2020
Reviewers invited
Invitations sent on 17 Sep, 2020
Submission checks complete
On 16 Sep, 2020
Editor invited
On 16 Sep, 2020
No comments provided
Editorial decision: Major revision
On 21 Aug, 2020
Review #1 received
Received 23 May, 2020
Reviewer #1 agreed
On 21 May, 2020
Reviewers invited
Invitations sent on 20 May, 2020
Editor assigned
On 11 May, 2020
Submission checks complete
On 10 May, 2020
Editor invited
On 10 May, 2020
First submitted
On 08 May, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Rheumatology
Learn more about our company.
This preprint is under consideration at Arthritis Research & Therapy. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement and SLE disease activity
Erwei Sun
Department of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5664-513X
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 22 Sep, 2020
Published
On 14 Oct, 2020
No community comments so far
Editorial decision: Accept
On 23 Sep, 2020
Review #1 received
Received 22 Sep, 2020
Reviewer #1 agreed
On 18 Sep, 2020
Editor assigned
On 17 Sep, 2020
Reviewers invited
Invitations sent on 17 Sep, 2020
Submission checks complete
On 16 Sep, 2020
Editor invited
On 16 Sep, 2020
No comments provided
Editorial decision: Major revision
On 21 Aug, 2020
Review #1 received
Received 23 May, 2020
Reviewer #1 agreed
On 21 May, 2020
Reviewers invited
Invitations sent on 20 May, 2020
Editor assigned
On 11 May, 2020
Submission checks complete
On 10 May, 2020
Editor invited
On 10 May, 2020
First submitted
On 08 May, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Rheumatology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Arthritis Research & Therapy.
Background: Necroptosis is a form of regulated necrosis that is involved in various autoimmune diseases. Mixed lineage kinase domain-like pseudokinase (MLKL) has been identified as a key executor of necroptosis, however, the significance of MLKL in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) has not been investigated. In this study, we aimed to determine the mRNA level of MLKL in PBMCs and examine its relationship with clinical features and serological parameters in SLE.
Methods: Real-time transcription-polymerase chain reaction analysis (RT-PCR) was used to determine expression of MLKL mRNA in PBMCs from 59 patients with SLE, 25 patients with rheumatoid arthritis (RA) and 30 age- and sex-matched healthy controls(HC). Spearman's correlation test was performed to assess the correlation of MLKL mRNA with clinical variables. The receiver operating characteristic curve (ROC) was created to evaluate the diagnostic value.
Results: Our results showed MLKL mRNA in PBMCs was upregulated in SLE patients compared to that in RA and HC individuals. SLE patients positive for anti-nuclear antibodies had significantly higher MLKL mRNA than antibody-negative patients. In SLE patients, MLKL mRNA was found to be upregulated in patients with lupus nephritis (LN) as compared with patients without LN, and also higher in active patients than in stable patients. MLKL mRNA level was significantly and positively correlated with c-reaction protein (CRP) (r=0.3577, p=0.0237), erythrocyte sedimentation rate (ESR) (r=0.4091, p=0.0043), serum immunoglobulin G (IgG) concentration (r=0.3546, p=0.0289) and the numbers of positive antinuclear antibodies (ANAs) (r=0.3945, p=0.0432). ROC analysis showed that MLKL mRNA in PBMCs had an area under the curve of 0.9277 (95% CI 0.8779 - 0.9775, p<0.001) to discriminate SLE from controls.
Conclusions: These results suggest that increased MLKL mRNA level in the PBMCs of SLE patients is correlated with renal involvement and disease activity, identifying a subgroup of patients with SLE or LN who may benefit from early diagnosis and therapies targeting MLKL.
Figure 1
Figure 2
Figure 3
Figure 4