Anti-alpha-actinin Antibodies and Lupus Nephritis Activity

NCT07505576 | Not Yet Recruiting

• 1 other identifier: AAALN
• Study Type: observational
• Target: 96
• Locations: 0 countries
• Sites: N/A

Brief Summary

Lupus nephritis (LN) develops in 30-60% of systemic lupus erythematosus (SLE) patients and remains a leading cause of morbidity, with 10-30% progressing to end-stage renal disease within 15 years. The International Society of Nephrology/Renal Pathology Society (ISN/RPS) classifies LN histologically, with proliferative forms (Classes III/IV) carrying the poorest prognosis.

Conditions

Lupus Nephritis

Outcome Measures

Primary Outcomes (2)

• evaluate associations between anti-alpha-actinin antibody levels and specific histological features of active LN

  To evaluate associations between anti-alpha-actinin antibody levels and specific histological features of active LN, including endocapillary hypercellularity, fibrinoid necrosis, and cellular crescents.

  36 months

• measure serum anti-alpha-actinin antibody levels in patients with biopsy-proven active lupus nephritis

  To measure serum anti-alpha-actinin antibody levels in patients with biopsy-proven active lupus nephritis and assess their correlation with the NIH histopathological activity index.

  36 months

Study Arms (3)

LN group

1. Adult patients (≥ 18 and \> 60 years) of either sex. 2. Fulfill the 2019 EULAR/ACR Classification Criteria for Systemic Lupus Erythematosus (SLE) \[11\]. 3. Diagnosis of active lupus nephritis requiring a renal biopsy as per standard clinical indications (e.g., proteinuria ≥ 0.5 g/24h, active urinary sediment, unexplained rise in serum creatinine). 4. Availability of an adequate renal biopsy specimen for histopathological evaluation according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2018 classification. 5. Renal biopsy performed within 3 months prior to enrollment, and patient has not received induction immunosuppressive therapy (cyclophosphamide, mycophenolate mofetil, or calcineurin inhibitors) in the period between biopsy and enrollment. 6. Provision of written informed consent.

Other: renal biopsy; Diagnostic Test: serum anti-alpha-actinin antibodies; Diagnostic Test: CBC, serum creatinine and urea, estimated GFR, ESR, CRP, urine analysis, ANA, anti dsDNA, C3 & C4, serum albumin, 24-hrs urinary protein, and U. ACR

SLE without nephritis

Patients meeting SLE criteria without any clinical or laboratory evidence of renal involvement (normal urinalysis, proteinuria \< 0.3 g/24h, normal serum creatinine).

Diagnostic Test: serum anti-alpha-actinin antibodies; Diagnostic Test: CBC, serum creatinine and urea, estimated GFR, ESR, CRP, urine analysis, ANA, anti dsDNA, C3 & C4, serum albumin, 24-hrs urinary protein, and U. ACR

Healthy controls

Age- and sex-matched healthy individuals with no history of autoimmune disease, normal urinalysis, and negative autoantibodies (ANA, anti-dsDNA).

Diagnostic Test: serum anti-alpha-actinin antibodies; Diagnostic Test: CBC, serum creatinine and urea, estimated GFR, ESR, CRP, urine analysis, ANA, anti dsDNA, C3 & C4, serum albumin, 24-hrs urinary protein, and U. ACR

Interventions

renal biopsy OTHER

Renal biopsy specimens will be evaluated by light microscopy and will be pathologically classified according to the 2003 International Society of Nephrology/ Renal Pathology Society classification (ISN/RPS Classification) as minimal mesangial (class I), mesangial proliferative LN (class II), focal LN (class III), diffuse LN (class IV), membranous LN (class V) and advanced sclerosis (class VI)

LN group

serum anti-alpha-actinin antibodies DIAGNOSTIC_TEST

Serum sample should be collected into a serum separator tube. After clotting for 2 hours at room temperature or overnight at 4°C, and then centrifuging at 1000 × g for 20 minutes. Assay freshly prepared serum immediately or store samples in aliquot at -20°C or -80°C for later use. Avoid repeated freeze-thaw cycles.

Healthy controls; LN group; SLE without nephritis

CBC, serum creatinine and urea, estimated GFR, ESR, CRP, urine analysis, ANA, anti dsDNA, C3 & C4, serum albumin, 24-hrs urinary protein, and U. ACR DIAGNOSTIC_TEST

Laboratory tests including, complete blood count (CBC, serum creatinine and urea and estimated GFR according to CKD-EPI and KDIGO;2024, urine analysis, C-reactive protein (CRP), Erythrocyte Sedimination Rate (ESR), anti-nuclear antibodies (ANA), serum albumin, serum complement (C3 and C4) ,anti-double stranded deoxyribonucleic acid (anti-dsDNA), 24-hrs urinary protein and urinary albumin:creatinine ratio (U. ACR).

Healthy controls; LN group; SLE without nephritis

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

1. Inclusion criteria for LN group: 1. Adult patients (≥ 18 and \> 60 years) of either sex. 2. Fulfill the 2019 EULAR/ACR Classification Criteria for Systemic Lupus Erythematosus (SLE) \[11\]. 3. Diagnosis of active lupus nephritis requiring a renal biopsy as per standard clinical indications (e.g., proteinuria ≥ 0.5 g/24h, active urinary sediment, unexplained rise in serum creatinine). 2. Exclusion criteria: Participants will be excluded if ANY of the following criteria apply: 1. Other Kidney Diseases: * Presence of, or suspicion of, any other primary or significant secondary kidney disease unrelated to SLE (e.g., diabetic nephropathy, hypertensive nephrosclerosis, IgA nephropathy, significant drug-induced nephrotoxicity, rheumatoid arthritis, positive HBs antigen or HCV antibody). 2. Confounding Clinical Conditions: * Presence of an active or recent major infection (e.g., sepsis, pneumonia, UTI) at the time of enrollment, as infection can significantly alter immune markers.

You may qualify if:

• Adult patients (≥ 18 and \> 60 years) of either sex.
• Fulfill the 2019 EULAR/ACR Classification Criteria for Systemic Lupus Erythematosus (SLE).
• Diagnosis of active lupus nephritis requiring a renal biopsy as per standard clinical indications (e.g., proteinuria ≥ 0.5 g/24h, active urinary sediment, unexplained rise in serum creatinine).
• Availability of an adequate renal biopsy specimen for histopathological evaluation according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2018 classification.
• Renal biopsy performed within 3 months prior to enrollment, and patient has not received induction immunosuppressive therapy (cyclophosphamide, mycophenolate mofetil, or calcineurin inhibitors) in the period between biopsy and enrollment.
• Provision of written informed consent.
• <!-- -->
• SLE without nephritis: Patients meeting SLE criteria without any clinical or laboratory evidence of renal involvement (normal urinalysis, proteinuria \< 0.3 g/24h, normal serum creatinine).
• Healthy controls: Age- and sex-matched healthy individuals with no history of autoimmune disease, normal urinalysis, and negative autoantibodies (ANA, anti-dsDNA).

You may not qualify if:

• Participants will be excluded if ANY of the following criteria apply:
• <!-- -->
• Other Kidney Diseases:
• Presence of, or suspicion of, any other primary or significant secondary kidney disease unrelated to SLE (e.g., diabetic nephropathy, hypertensive nephrosclerosis, IgA nephropathy, significant drug-induced nephrotoxicity, rheumatoid arthritis, positive HBs antigen or HCV antibody).
• Confounding Clinical Conditions:
• Presence of an active or recent major infection (e.g., sepsis, pneumonia, UTI) at the time of enrollment, as infection can significantly alter immune markers.
• Presence of advanced chronic kidney disease (CKD Stage 4 or 5) predating the diagnosis of SLE.
• Pregnancy or lactation.
• Confounding Medications:
• Receipt of high-dose corticosteroids (\> 20 mg/day of prednisone or equivalent) or any potent immunosuppressive agent (e.g., cyclophosphamide, mycophenolate mofetil, rituximab) within 4 weeks prior to the renal biopsy and blood sampling).

Sponsors & Collaborators

• Assiut University: lead

Related Publications (7)

• Deocharan B, Qing X, Lichauco J, Putterman C. Alpha-actinin is a cross-reactive renal target for pathogenic anti-DNA antibodies. J Immunol. 2002 Mar 15;168(6):3072-8. doi: 10.4049/jimmunol.168.6.3072.

  PMID: 11884481 BACKGROUND

• Tsai CY, Li KJ, Shen CY, Lu CH, Lee HT, Wu TH, Ng YY, Tsao YP, Hsieh SC, Yu CL. Decipher the Immunopathological Mechanisms and Set Up Potential Therapeutic Strategies for Patients with Lupus Nephritis. Int J Mol Sci. 2023 Jun 13;24(12):10066. doi: 10.3390/ijms241210066.

  PMID: 37373215 BACKGROUND

• He S, Zhang J, Wang X, Qi Z, Zhou Z, Wang Y, Xu S, Li D, Ye X, Liu Z, Hao X, Zhao Y, Wang R. Organoid Modeling and Single-Cell Profiling Reveal Smooth Muscle Cell Migration in Moyamoya Disease. Commun Biol. 2026 Jan 7;9(1):198. doi: 10.1038/s42003-025-09476-9.

  PMID: 41501150 BACKGROUND

• Aringer M. EULAR/ACR classification criteria for SLE. Semin Arthritis Rheum. 2019 Dec;49(3S):S14-S17. doi: 10.1016/j.semarthrit.2019.09.009.

  PMID: 31779843 BACKGROUND

• Alduraibi FK, Tsokos GC. Lupus Nephritis Biomarkers: A Critical Review. Int J Mol Sci. 2024 Jan 9;25(2):805. doi: 10.3390/ijms25020805.

  PMID: 38255879 BACKGROUND

• Gladman DD, Ibanez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 2002 Feb;29(2):288-91.

  PMID: 11838846 BACKGROUND

• Almaani S, Meara A, Rovin BH. Update on Lupus Nephritis. Clin J Am Soc Nephrol. 2017 May 8;12(5):825-835. doi: 10.2215/CJN.05780616. Epub 2016 Nov 7.

  PMID: 27821390 BACKGROUND

MeSH Terms

Conditions

Lupus Nephritis

Interventions

Blood Cell Count; Blood Sedimentation; Urinalysis

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cell Count; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Hematologic Tests; Investigative Techniques; Cell Physiological Phenomena; Blood Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Clinical Chemistry Tests; Diagnostic Techniques, Urological

Central Study Contacts

Essam Mohamed Abdel Aziz, MD

CONTACT

+201009699081; essam.abdelaziz@med.aun.edu.eg

Mohammed Abbas Sobh, MD

CONTACT

+201067663269; hamed.msobh@aun.edu.eg

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 23, 2026
• First Posted: April 1, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: April 1, 2026

Record last verified: 2026-03