CRISPR-targeted microbiome modulation in rare Henoch-Schonlein purpura IgA nephropathy-gastritis - insights into the gut-kidney axis

Sep 29, 2026

Letter to the editor discusses CRISPR-targeted microbiome modulation as a potential therapeutic direction for rare overlap disease involving Henoch-Schonlein purpura, HSP nephritis and IgA nephropathy with gastritis. It links gastric mucosal deposition of galactose-deficient IgA1 complexes and dysbiosis to gut–kidney immune dysfunction, explains the gut-kidney axis as a therapeutic target, and highlights Gd-IgA1 as a cross-organ biomarker for earlier detection and monitoring. It contrasts standard immunosuppression with emerging microbiome approaches and argues for biomarker-led clinical monitoring to prevent progression to chronic kidney disease.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages2

Reading Time5 min

AccessFree to download

Letter to the Editor

Gut–kidney axis and IgA1 (Gd-IgA1) mechanism

CRISPR-modulated microbiome therapy and engineered Akkermansia

Biomarker-led monitoring and clinical implications

Conclusion

Letter to the Editor CRISPR-targeted microbiome modulation in rare Henoch-Schonlein purpura IgA nephropathygastritis: insights into the gut-kidney axis Pakeeza Saif, MBBSa , Muhammad Tausif, MBBSb , Mahnoor Fatima, MBBSc ,*, Abdullah Imtiaz, MBBSd , Muammar Hassan, MBBSa To the Editor, Henoch-Schonlein purpura (HSP), most notably HSP nephritis (HSPN), is an autoimmune vasculitis that primarily targets small vessels in the skin, joints, gastrointestinal tract, and kidneys, causing significant issues in pediatric patients because of the risk of progression into chronic kidney disease (CKD) . Recent mucosal biopsies show the deposition of galactose-deficient Immunoglobulin A1 (Gd-IgA1) complexes in the gastric mucosa, which strengthens the gut mucosa as a site of immune dysregulation contributing to systemic mucosal flare-ups and renal damage in HSPN-IgA Nephropathy (IgAN) overlap syndromes[1] . The gut-kidney axis is currently being acknowledged as a critical therapeutic target to inhibit ongoing vasculitic progression and topreserve renal function[2]. This letter is in line with the TITAN Guidelines on the need for transparency in AI use in health care[3] . Aberrant mucosal immune homeostasis augments the production of aberrantly glycosylated IgA, especially an increase in Gd-IgA1, which forms circulating immune complexes that deposit within the renal mesangium, leading to inflammation and causing the pathogenic link between gut microbiota dysbiosis and IgAN. The altered intestinal barrier and dysregulated mucosal B-cell responses due to dysbiosis are involved in this process [4] . Currently, available standard therapies have included immunosuppression, but there is increasing evidence to promote microbiome-targeted approaches[2] . Most importantly, there is significant potential for using CRISPR gene editing to alter the composition and functioning of gut microbiota[5] . In this context, engineered Akkermansia species aDepartment of Medicine, King Edward Medical University, Lahore, Pakistan, bDepartment of Medicine, Mayo Hospital, Lahore, Pakistan, cDepartment of Medicine, Shaheed Ziaur Rahman Medical College, Rajshahi Medical University, Bangladesh and dDepartment of Medicine, Wah Medical College, Wah Cantt, Pakistan Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. *Corresponding author. Address: Department of Medicine, Shaheed Ziaur Rahman Medical College, Rajshahi Medical University, Ladies Hostel, Bogura 5800, Bangladesh. Tel.: +[880 01972635581. E-mail: mahnoorzahid786@gmail.com](880 01972635581. E-mail: mahnoorzahid786@gmail.com)[ ](880 01972635581. E-mail: mahnoorzahid786@gmail.com)(M. Fatima). Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Annals of Medicine & Surgery (2026) 88:1090–1091 Received 23 September 2025; Accepted 18 November 2025 Published online 3 December 2025 [http://dx.doi.org/10.1097/MS9.0000000000004466](http://dx.doi.org/10.1097/MS9.0000000000004466) have been proposed to remodel glycans into the mucosal habitat, mitigating purpuric flares by restoring barrier integrity and reducing pathogenic IgA complex formation[1,4,5] . Arthralgia that occurs in HSP or IgA vasculitis often mimics symptoms seen in inflammatory bowel disease (IBD), complicating clinical differentiation[6]. Thus, serum Gd-IgA1 has been proposed as a cross-organ biomarker reflecting shared immunopathological pathways, allowing earlier identification of systemic involvement and tailoring strategies for intervention. The importance of this particular biomarker is underscored in pediatric vasculitis, where being able to recognize and treat it promptly may prevent progression toward irreversible renal da

FAQs

What role does the gut–kidney axis play in HSPN and IgA nephropathy overlap with gastritis?

The letter frames the gut–kidney axis as a key therapeutic target because mucosal immune dysregulation and microbiome dysbiosis can drive systemic progression, contributing to renal damage in overlapping HSPN/IgAN disease.

Why is galactose-deficient IgA1 (Gd-IgA1) emphasized?

Gd-IgA1 complexes are described as deposited in gastric mucosa and as a serum biomarker reflecting shared immunopathological pathways. This supports earlier identification of multi-organ involvement and tailoring intervention strategies.

How does CRISPR-targeted microbiome therapy relate to treatment beyond standard immunosuppression?

The discussion argues that microbiome-targeted approaches may complement or extend standard immunosuppression, including using CRISPR gene editing to remodel the composition and function of gut microbiota such as engineered Akkermansia strains.

Sep 29, 2026

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