Detection of Macrophage Colony Stimulating Factor in Systemic Lupus Erythematosus Patients and its Relation to Disease Activity and Severity

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Introduction
Persistent inflammation and the generation of autoantibodies stand out as prominent characteristics of systemic lupus erythematosus (SLE) [1,2].The induction of tissue damage and concurrent health conditions, particularly those related to kidney participation, can be attributed to either the treatment for SLE or the condition itself [3].Individuals with SLE may encounter signs such as microvascular involvement, which emerges as a notable feature [4].
Employing nailfold capillaroscopy (NFC) may be advantageous in evaluating the changes in microvascular patterns evident in individuals diagnosed with SLE [5].The involvement of the kidneys presents as a significant manifestation of SLE, potentially resulting in an unfavorable prognosis and the development of end-stage kidney failure [6].
Renal biopsy continues to serve as the primary method for diagnosing lupus nephritis, while the availability of validated biomarkers for tracking the progression of SLE remains limited [7].
Consequently, there exists a pressing necessity for the recognition of innovative biomarkers capable of evaluating renal engagement and disease activity.The sequence of inflammatory reactions sparked by the disruption of the immune system's equilibrium and the identification of self-antigens sets in motion a recurrent cycle of immune cell activation in SLE.Individuals affected by SLE are demonstrating a growing prevalence of abnormalities in both the composition and operation of monocytes and macrophages [8,9].
When in an adequate state, macrophages and monocytes are fundamental segments of the innate immune system.They perform a variety of immunological tasks, including presenting antigens, phagocytosing particles, and generating cytokines [10].Activated by GM-CSF and TNF-α, macrophages-also referred to as activated macrophages-show dual roles in the germ defensive framework and inflammation.The cytokines released by these activated macrophages include IL-6 and TNF-α.
On the other hand, IL-4 and M-CSF cause a specific subgroup of macrophages-referred to as M2 macrophages-to polarize.The capacity of these M2 macrophages to produce cytokines that reduce inflammation, such as IL-10, sets them apart [11,12].Additionally, there exists a connection between macrophages showcasing the soluble urokinase plasminogen activator receptor (uPAR) and those characterized by the M2 phenotype [13].Moreover, M-CSF and Interleukine-34 operate through a shared receptor, guiding macrophages toward a phenotype responsible for regulating M2 [14].
This study aims to analyze the concentrations of M-CSF in SLE patients' serum, exploring its correlation with disease progress, renal involvement, effects on peripheral blood vessels, and other related factors.

Subjects
The research was carried out within the inpatient and outpatient departments of the rheumatology department at Fayoum University Hospital.Fifty individuals diagnosed with SLE, meeting the 2019 EULAR/ACR criteria, were enrolled in the study.Exclusions comprised individuals with cancer, infections, or alternative autoimmune conditions [15].
Furthermore, the study incorporated 50 healthy individuals without any previous record of systemic or chronic autoimmune conditions as control subjects.

Methods
A comprehensive set of laboratory for gauging the progression of the illness [17].
The assessment of peripheral vascular affection and its relationship to serum M-CSF levels was done using nailfold capillaroscopy.

Results
This study comprised thirty-seven female participants (accounting for 94%) and three male participants (representing 6%) diagnosed with SLE.The age range among the study's participants spanned from 18 to 56 years, with a mean age of 33.9 ±10.8 years.In contrast, the control group exhibited an age range of 21 to 52 years, with a mean age of 31.1 ±8.7 years.This results in the development of antibodies against nuclear antigens, the initiation of inflammatory processes, and the synthesis of immunological complexes.After that, these complexes are placed inside tissues [20].
A wealth of documentation brings to light the impact that innate immune pathways have on the pathophysiology of SLE.Many studies have found abnormalities in macrophage recruitment, polarization, phagocytic efficiency, and excretion that are exacerbated by a high cytokine load [21].The cytokine known as M.
CSF/CSF-1 plays an important role in the advancement, sustenance, activation, and function of the monocyte-macrophage lineage [22].
There is a wealth of supporting data showing that innate immune pathways serve a key involvement in the pathogenesis of SLE.Funding: This study is not funded.

Conflicts of Interest:
All authors declare they have no conflicts of interest.
Based on our findings, a statistically notable contrast emerges in the concentration levels of M-CSF among distinct renal biopsy groups.Notably, Class I and Class II exhibited diminished M-CSF levels, whereas higher concentrations were evident in Classes V, IV, and III.The inconsistencies allude to a conceivable link between the extent of kidney degradation and the harshness of nephritis.In line with our discoveries, a separate inspection noted that levels of M-CSF in the serum and urine of SLE patients were most preeminent in class IV, reasonably eminent in class III, and eminent to the lowest degree in class II.These findings were congruent with the notion that M-CSF expression is heightened in class IV renal tubules compared to class II renal tubules in SLE patients [30].Conclusion Our preliminary inquiry, marking the inaugural utilization of NFC in this context, failed to reveal any link between the levels of M-CSF in circulation and the occurrence of peripheral vascular impediments.The limited sample size in our study underscores the need for further research to confirm the relationship between M. CSF levels and other clinical features of the disease.Additionally, due to the cross-sectional research design, only enrolled patients had access to follow-up data, highlighting the necessity for longitudinal studies to assess the predictive efficacy of M-CSF in the early detection of renal flare-ups.Furthermore, although the effects of medications were not examined in this investigation, the use of immunosuppressive and anti-inflammatory medications in SLE patients may have influenced M-CSF levels.Eventually, our findings revealed greater levels of M. CSF in SLE patients.Besides, patients in classes V and IV had greater M. CSF levels than those in classes I and II, suggesting a possible link to renal disease severity.Ethical approval: Following the provision of informed written consent by both patients and controls at the outset, the project received approval from the Ethics Committee (Reference: M588) of the Faculty of Medicine's Biomedical Research at Fayoum University.

Table 1 :
Frequency of different clinical manifestations among systemic lupus erythematosus cases.

Table 3 and
Figure 1.

Table 2 :
Frequency of laboratory investigations of systemic lupus erythematosus patients under the study.

Figure 1 :
Nailfold capillaroscope findings among our SLE patients.Arrows refer to microhemorrhages, black circles refer to dilated capillaries, squares refer to branching capillaries, rods refer to crossed loops and blue circles refer to tortous loops.

Table 4 ) . Table 4 :
Macrophage colony-stimulating factor levels in systemic lupus erythematosus patients and controls.
class V -LN cases demonstrated the most elevated concentrations, while class I cases presented the least values, as illustrated in

Table 5 .Table 5 :
Relation of macrophage colony-stimulating factor levels and renal biopsy findings among SLE cases with lupus nephritis.

Table 6 :
Comparison of macrophage colony stimulating factor levels with nailfold capillaroscopy findings and SLEDAI-SELENA Score among SLE cases.