B-cell and plasma-cell causality: references

Recommended reviews and the clinical evidence behind the ranking

Status markers

• ✅ Checked claim. The narrow statement used here was checked against a source abstract, caption or specified full-text passage. The entry states the access level; this is not a claim of full-paper appraisal.
• ⚠️ Partially checked. Relevant information was retrieved, but the interpretation requires additional source checks.
• ❌ Not checked. A reading task remains open.

Searches on 22 September 2026 used PubMed and publisher pages, with terms combining B-cell/plasma-cell targeting, reviews, indication names, rituximab response predictors, and named trials. Recent searches specifically checked 2025–2026 SLE, myasthenia and Sjögren’s developments. This is a targeted selection, without systematic screening or a formal risk-of-bias assessment. Some findings were retrieved as indexed excerpts of primary abstracts when direct page opening failed. Such entries are labelled accordingly.

The evidence review contains the disease ranking. Its ordering and patient-interpretation framework are the project’s synthesis, not a ranking published by one of these sources.

Reading queue

1. ⚠️ Abeles 2024, Yuan and Xu 2026, and Schett 2024. Read the complete reviews against the distinction between antibody-mediated and other B-cell functions.
2. ⚠️ Stockfelt 2025, then Wincup 2026. Resolve which predictors of rituximab benefit have replication and which are associations after treatment.
3. ⚠️ Fooksman 2024, Halliley 2015 and KDIGO 2026. Separate long-lived plasma-cell function from CD19 status or marrow residence alone.
4. ⚠️ SSc fibrosis review, 2026. Identify the evidence that immune targeting changes organ disease versus established fibrotic damage.
5. ⚠️ R4RA and STRAP. Appraise comparative biomarker effects, validation cohorts and the evidence that profiling improves a treatment decision.
6. ⚠️ Recent modality studies. Compare full methods for REGENCY, ALLEGORY, MINT and Descartes-08 before using them in a quantitative comparison.

Reviews to prioritize

Abeles et al. 2024 — B Cell–Directed Therapy in Autoimmunity

✅ Abstract checked; full review pending. Annual Review of Immunology 42:103–126. Journal article.

Start here for the cross-disease framework: antibodies, antigen presentation and cytokine functions, and why clinical efficacy varies by indication. The publisher abstract and bibliography were accessible; detailed disease claims in this project use the additional trials and reviews below.

Yuan and Xu 2026 — Translating B-Cell and Plasma-Cell Targeting from Oncology to Autoimmunity: Modalities, Quantitative Bridging, and a Development Roadmap

✅ Abstract and indexed mechanistic passages checked; full review pending. Clinical Pharmacology & Therapeutics 120:598–613. DOI: 10.1002/cpt.70352. PubMed · PMC.

A close match to this project: compares dependence on B-cell precursors, tissue inflammation and established plasma-cell populations, then relates those hypotheses to target coverage and treatment modality. Its proposed classification and quantitative development approach need validation before they can guide individual treatment selection.

Floege et al. 2026 — Targeting B cells in immune-mediated kidney diseases: conclusions from a KDIGO Controversies Conference

✅ Abstract and indexed plasma-cell and disease-comparison passages checked. Kidney International 110:548–565. KDIGO means Kidney Disease: Improving Global Outcomes. Journal · Conference report PDF.

Prioritize for kidney disease comparisons and the distinction between CD19 expression and plasma-cell lifespan. Both CD19-positive and CD19-negative plasma-cell populations can persist. This conference synthesis identifies research gaps; it is not evidence that broader depletion always improves outcomes.

Schett et al. 2024 — B-cell depletion in autoimmune diseases

✅ Abstract checked; full review pending. Annals of the Rheumatic Diseases 83:1409–1420. PubMed. DOI: 10.1136/ard-2024-225727.

Read for antibody depletion versus engineered-cell approaches and the proposal that deeper depletion can change remission durability. Useful companion to Abeles; its synthesis is not comparative proof of CAR-T superiority.

Stockfelt, Teng and Vital 2025 — Opportunities and limitations of B cell depletion approaches in SLE

✅ Publisher abstract and summary points checked. Nature Reviews Rheumatology 21:111–126. Journal article.

Prioritize for rituximab nonresponse: residual cells, immunogenicity, B-cell-activating factor (BAFF), and alternative inflammatory mechanisms. Full text was subscription-restricted. Subsequent trials below update its clinical context.

Wincup et al. 2026 — The why, what, who and when of B cell depletion in systemic lupus erythematosus: biological rationale, patient stratification and evolving therapeutic modalities

✅ Indexed abstract checked; full-text review pending. Rheumatology. PubMed · PMC full-text link.

The closest match to this project’s patient-selection question. Read for compartment, modality and treatment timing. Direct PMC retrieval encountered a browser challenge; no full-paper verification is claimed.

Fooksman, Jing and Park 2024 — New insights into the ontogeny, diversity, maturation and survival of long-lived plasma cells

✅ Publisher abstract checked; full review pending. Nature Reviews Immunology 24:461–470. Journal article.

Read for how plasma cells acquire longevity and depend on survival conditions. Supports the distinction between an antibody-producing phenotype and durable persistence; it is not a clinical test for BCMA response.

Lee, Rojas and Gommerman 2021 — B cell depletion therapies in autoimmune disease: advances and mechanistic insights

✅ Abstract and indexed mechanistic passages checked. Nature Reviews Drug Discovery 20:179–199. Journal article · PMC.

A foundational review of benefits despite persistence of antibodies and plasma cells. Use for mechanism, with newer trials for efficacy. A later author correction is linked from the journal record; check the corrected full text before extracting figures or detailed tables.

Junt et al. 2025 — Defining immune reset: achieving sustained remission in autoimmune diseases

✅ Publisher abstract checked; full perspective pending. Nature Reviews Immunology 25:528–541. Journal article.

A perspective on what durable remission and immune reconstitution would need to show. Read when distinguishing a mechanistic hypothesis from demonstrated long-term benefit after a particular modality.

Mechanisms of fibrotic tissue remodelling: insights from systemic sclerosis, 2026

✅ Publisher abstract and summary points checked. Nature Reviews Rheumatology 22:221–238. Journal article.

The SSc counterweight to an exclusively B-cell explanation: vascular injury, immune interactions and tissue-intrinsic fibrosis mechanisms. Full-text review is needed for specific organ and patient-selection claims.

Kawano 2025 — IgG4-related Disease: Recent Topics on Immunological Aspects of This Disorder and Their Application in New Treatment Strategies

✅ Abstract checked. Internal Medicine 64:31–39. PubMed.

Read for tertiary lymphoid tissue and interactions of B cells with T cells and other lesion-forming populations. A response to CD19 depletion need not make serum IgG4 concentration the sole pathogenic mechanism.

Rituximab for myasthenia gravis, 2025 — Cochrane review

✅ Indexed review methods and conclusions checked. Full text.

Compares RINOMAX and BeatMG and exposes the limits of pooling their populations. MuSK-specific rituximab evidence is largely outside those randomized studies. Read with the newer CD19 and BCMA trials below, not as a complete current inventory of myasthenia therapies.

Rituximab in the treatment of immune thrombocytopenia: what is the role of this agent in 2019?

✅ Indexed clinical and durability passages checked. Haematologica. Review.

Useful for heterogeneity, initial responses and loss of response over time. Its age limits its use for current treatment sequencing; this project uses it for interpreting rituximab, not for current guideline recommendations.

Targeted immunosuppressive and immunomodulatory therapies for idiopathic inflammatory myopathies, 2025 — Cochrane review

✅ Indexed rituximab analysis checked. Review.

Read for the low certainty of comparative rituximab evidence and the design limitations of RIM. The pooled label “myositis” conceals clinically different subgroups.

Studies supporting disease and target comparisons

Halliley et al. 2015 — human long-lived plasma cells

✅ Indexed abstract and results passages checked. Immunity 43:132–145. Study.

Identifies a CD19-negative marrow plasma-cell subset containing durable antiviral antibody production. Supports a population that CD19 targeting can spare; it does not classify every autoimmune plasma cell by longevity.

Joly et al. 2017 — Ritux 3, pemphigus

✅ Primary abstract checked. Lancet. PubMed.

Randomized open-label comparison of rituximab plus short-course prednisone versus prednisone alone. Month-24 complete remission off therapy was 41/46 versus 15/44. The result applies to the treatment strategies studied.

Cree et al. 2019 — N-MOmentum, NMOSD

✅ Primary abstract result checked. Lancet 394:1352–1363. Trial.

Inebilizumab versus placebo; attacks in 21/174 versus 22/56 during the randomized period. Those are overall trial denominators, not an exclusively AQP4-positive-subgroup estimate. Interpretation emphasizes AQP4-positive disease; extract subtype-specific results before estimating subgroup benefit.

Stone et al. 2010 — RAVE, ANCA-associated vasculitis

✅ Primary abstract checked. New England Journal of Medicine 363:221–232. Trial.

Randomized noninferiority trial in 197 ANCA-positive patients. Six-month remission off prednisone: 64% with rituximab versus 53% with the cyclophosphamide-based comparator. Noninferiority does not establish universal superiority; glucocorticoids accompanied induction.

Stone et al. 2025 — MITIGATE, IgG4-RD

✅ Primary abstract checked. New England Journal of Medicine 392:1168–1177; online November 2024. Trial.

Phase 3 CD19-antibody evidence used in the review’s flare comparison. The hazard ratio was 0.13 (95% confidence interval 0.06–0.28). Serious adverse events were reported in 18% versus 9%; compare benefit and harm within this population, not with unrelated trial populations.

Nowak et al. 2025 — MINT, generalized MG

✅ Primary abstract checked. New England Journal of Medicine 392:2309–2320. Trial.

Randomized 238 AChR- or MuSK-antibody-positive participants. The MG-ADL result used in the review is a week-26 between-group effect. Subtype-specific precision and longer-term durability require the full tables; do not infer equivalence of benefit across antibody subgroups.

Hauser et al. 2017 — OPERA I and II, relapsing MS

✅ Primary abstract checked. New England Journal of Medicine 376:221–234. PubMed.

Two trials randomized 821 and 835 participants. Ocrelizumab reduced annualized relapses relative to interferon beta-1a. Supports clinical B-cell involvement; the trials do not isolate antibody production as the required mechanism.

Cohen et al. 2006 — REFLEX, RA

✅ Primary abstract checked. Arthritis & Rheumatism 54:2793–2806. PubMed.

The review preserves the week-24 ACR20 endpoint, anti-TNF inadequate-responder population and methotrexate background. Do not relabel this improvement rate as remission or extrapolate it to an unselected RA population.

Updated consensus statement on rituximab in RA, 2011

✅ Indexed serostatus passages checked. Consensus review.

Supports rheumatoid factor/anticitrullinated protein antibody enrichment. Used for this historical evidence, not as current prescribing guidance.

Furie et al. 2025 — REGENCY, lupus nephritis

✅ Primary abstract checked. New England Journal of Medicine 392:1471–1483. Trial.

271 randomized patients; the review reports complete renal response at week 76. Both groups received standard therapy. More serious adverse events, chiefly infections and COVID-19-related events, occurred with obinutuzumab. This was not a rituximab comparison.

Furie et al. 2026 — ALLEGORY, nonrenal SLE

✅ Indexed primary abstract checked. New England Journal of Medicine 395:243–254. PubMed · Journal.

Supports the reported week-52 SRI-4 comparison with standard therapy in both arms. Proliferative or membranous lupus nephritis was excluded. The primary abstract was retrieved through search; direct publisher retrieval failed. Detailed endpoint handling and subgroup effects remain to be extracted.

Ebata et al. 2021 — DESIRES, SSc

✅ Primary abstract checked. Lancet Rheumatology 3:e489–e497. PubMed.

Randomized, blinded, placebo-controlled trial supporting the skin-score effect reported in the review. Enrollment required a modified Rodnan skin score of at least 10. No inference of efficacy across all SSc organs is made here.

DESIRES predictor analysis, 2022

✅ Abstract design checked; detailed predictor appraisal pending. PubMed.

Post hoc analysis considered 27 baseline factors in 54 participants. A small exploratory model cannot itself establish a validated patient-selection rule.

Bowman et al. 2017 — TRACTISS, Sjögren’s

✅ Primary abstract and indexed results checked. Arthritis & Rheumatology 69:1440–1450. Trial · Author manuscript and repository abstract.

Anti-Ro-positive participants with fatigue and oral dryness; the primary symptom endpoint was not met. This constrains claims for rituximab symptom benefit, without resolving every systemic manifestation or other target.

Fervenza et al. 2019 — MENTOR, primary membranous nephropathy

✅ Indexed primary report results checked. New England Journal of Medicine 381:36–46. Trial.

Rituximab was noninferior to cyclosporine for inducing proteinuria remission at 12 months and superior for maintaining remission through 24 months. The maintenance result depends on the comparator regimen and follow-up; it is not a direct comparison of CD20 with CD19 or BCMA.

Lafayette et al. 2017 — rituximab in IgA nephropathy

✅ Primary abstract checked. Journal of the American Society of Nephrology 28:1306–1313. PubMed.

Open-label randomized study of 34 adults with proteinuria and impaired kidney function. Depletion without a renal or disease-associated antibody effect is a counterexample to using peripheral B-cell loss as a sufficient surrogate for benefit. The small trial does not test all disease stages or other targets.

Grader-Beck et al. 2025 — NEPTUNUS-1 and NEPTUNUS-2, Sjögren’s

✅ Meeting abstract checked; full journal appraisal pending. ACR abstract LB24.

Two randomized phase 3 studies reported positive week-48 systemic disease activity endpoints with monthly ianalumab. This antibody combines B-cell depletion with BAFF-receptor blockade. A full primary journal report was not located in this search; conference evidence remains labelled as such.

Patel et al. 2012 — long-term rituximab response in ITP

✅ Indexed primary results checked. Blood. Study.

Estimated five-year sustained treatment-free responses were approximately 21% in adults and 26% in children. This is long-term observational evidence, not a randomized comparison or an individual prediction model.

Oddis et al. 2013 — RIM, inflammatory myositis

✅ Primary abstract checked. Arthritis & Rheumatism 65:314–324. PubMed.

Early versus delayed rituximab, with 200 randomized participants. The primary comparison was negative even though many eventually improved. The latter observation cannot supply a placebo-adjusted response rate.

Patient stratification and emerging modalities

Humby et al. 2021 — R4RA

✅ Primary abstract and result table passages checked. Lancet. Full text.

Primary histology-based B-cell-poor comparison: no significant difference. The RNA-defined B-cell-poor comparison favoured tocilizumab. Preserve the classification method and analysis population when discussing a tissue test.

STRAP molecular profiling, 2025

✅ Indexed results and discussion checked; full prediction-model audit pending. Nature Communications 16:5374. Study.

Response-associated signatures support tissue stratification research. Shared B-cell gene modules in responses to more than one drug caution against equating a B-cell signature with specific dependence on rituximab. Assess validation and prospective utility before proposing implementation.

Müller et al. 2024 — CD19 CAR-T case series

✅ Primary abstract checked. New England Journal of Medicine 390:687–700. Study.

Fifteen patients spanning SLE, inflammatory myositis and SSc, treated after fludarabine/cyclophosphamide. Remission signals support investigation, but uncontrolled selection and conditioning prevent target-specific causal attribution and a comparative response estimate.

Feng et al. 2025 — dual CD19/BCMA CAR-T in SLE

✅ Publisher abstract checked. Nature Medicine 31:3725–3736. Study.

Fifteen patients with refractory SLE. Dual targeting and conditioning prevent isolation of the BCMA contribution. Tissue and clone interpretation is also tracked in imm-biopsy.

Bucci et al. 2025 — BCMA T-cell engager therapy

✅ Publisher summary checked; detailed letter and supplement pending. New England Journal of Medicine 393:1544–1547. Report.

Ten refractory autoimmune-disease patients receiving teclistamab. Clinical and serologic signals are hypothesis-generating; no comparator establishes superiority or identifies who benefits after CD20 depletion.

Vu et al. 2026 — Descartes-08 randomized phase 2b MG trial

✅ Full-text participant flow, endpoint and results passages checked. Nature Medicine 32:1131–1141. Trial.

The review distinguishes the randomized/safety population from the primary efficacy subset. Read the endpoint amendment and analysis-set rationale before using its effect size; background therapy also limits drug-free-remission claims. It is not a direct comparison with CD19 or CD20 treatment.

Unresolved source checks

• ❌ Full risk-of-bias and endpoint appraisal for the trials used in the ranking.
• ❌ Replicated, prospective patient-selection performance for RA synovial classifiers and SLE/SSc biomarkers.
• ❌ Direct target or modality comparisons specifically in documented rituximab nonresponders, including adequate tissue-depletion measurements.
• ❌ Detailed clinical subtypes within myositis and ITP, and a systematic search for newer results that would change their tier.
• ❌ Disease-specific BCMA evidence beyond the MG randomized trial and the early rheumatic-disease reports summarized here.