Obinutuzumab in Crescentic Anti-Glomerular Basement Membrane Disease with Linear IgG Deposition: A Case Report

Abstract

Introduction

Anti-glomerular basement membrane (anti-GBM) disease is a rare autoimmune vasculitis that often leads to rapidly progressive glomerulonephritis and poor renal prognosis. Standard treatment typically involves plasmapheresis, corticosteroids, and cyclophosphamide. However, the therapeutic role of obinutuzumab, a B-cell-depleting monoclonal antibody, remains under-explored in anti-GBM disease.

Case Presentation

We report a 20-year-old male with isolated renal anti-GBM disease following a dental infection, who presented with severe acute kidney injury (creatinine >700 μmol/L), high anti-GBM antibody titers, and crescentic glomerulonephritis on biopsy. Despite initial therapy with plasmapheresis, corticosteroids, and cyclophosphamide, renal function deteriorated. Obinutuzumab (500 mg IV) was administered as adjunct therapy, leading to rapid antibody clearance within 1 month. Remarkably, the patient achieved partial renal recovery and was dialysis-independent by 3 months, with stable stage 3 chronic kidney disease at 5-month follow-up.

Conclusion

This case underscores the potential role of obinutuzumab as an innovative adjunctive therapy in severe anti-GBM disease, even in patients with traditionally poor prognostic markers. Early and aggressive multimodal treatment, including B-cell targeting, may improve outcomes in selected cases.

Introduction

Anti-glomerular basement membrane (anti-GBM) disease is a rare but life-threatening autoimmune small-vessel vasculitis that most often presents as rapidly progressive glomerulonephritis (RPGN) and, in about half of cases, pulmonary hemorrhage [1]. It is caused by autoantibodies directed against the non-collagenous domain of type IV collagen (especially the α3(IV) chain) in glomerular and alveolar basement membranes [2]. These pathogenic IgG antibodies trigger intense inflammation, leading to severe damage in the kidneys and sometimes the lungs. The incidence of anti-GBM disease is low (approximately 1 per million persons per year), but the consequences are dire if not promptly treated – about two-thirds of patients progress to end-stage kidney disease requiring dialysis despite therapy [3]. Common signs include acute kidney injury with hematuria (often gross hematuria) and proteinuria, and when lungs are involved (the classic Goodpasture’s syndrome), patients may experience cough, hemoptysis, and pulmonary infiltrates [4].

The exact trigger for the loss of tolerance to the GBM antigen is not fully understood. A combination of genetic predisposition (such as HLA-DR15) and environmental exposures is thought to contribute. Notably, infections have been reported as potential triggers; for example, Goodpasture syndrome can sometimes develop after a viral or upper respiratory infection [5]. Exposure to tobacco smoke or inhaled hydrocarbons is also a known risk factor [6]. We present here a case of isolated renal anti-GBM disease in a young male, where the illness was preceded by a dental procedure and infection, potentially acting as a precipitating factor. The case is notable for its severe presentation and the use of aggressive therapy, including plasmapheresis, immunosuppression, and especially obinutuzumab, with partial renal recovery at follow-up.

Case Presentation

A 20-year-old male college student with no prior medical history developed fever and malaise 2 weeks after wisdom tooth extraction, for which he received a short course of amoxicillin and metronidazole. Two days post-op, he experienced persistent high fevers (38–39°C), chills, and a mild cough. One week later, he noticed tea-colored, frothy urine. No dysuria, flank pain, or urinary frequency was reported. Gross hematuria persisted for 10 days before he sought medical care. The CARE Checklist has been completed by the authors for this case report and is provided as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000552035).

Urinalysis showed 2+ protein and blood. Labs revealed leukocytosis, high CRP (142 mg/L), and acute kidney injury (creatinine 528 μmol/L; urea 20.3 mmol/L). Anti-GBM antibodies were markedly elevated (433.9 AU/mL), while ANCA, ANA, and infectious serologies were negative. Complement levels were normal. Presumptive diagnosis was anti-GBM disease causing RPGN, without lung involvement. The patient received three sessions of plasmapheresis, high-dose IV steroids (methylprednisolone 500 mg/day ×3 days), and one dose of IV cyclophosphamide (800 mg). Despite treatment, renal function worsened (creatinine peaked at 674 μmol/L), and hematuria persisted. Anti-GBM titers remained high. He was referred to a tertiary center for further care and biopsy.

Hospital Admission and Examination

On admission, he was stable, without respiratory symptoms or edema. Labs confirmed severe renal dysfunction (creatinine 701 μmol/L), mild anemia (Hb 10.4 g/dL), and persistent anti-GBM positivity. ANCA and ANA remained negative. Chest CT showed minor nodules and pleural effusions, but no signs of alveolar hemorrhage.

Renal Biopsy

Light microscopy of the renal specimen (12 glomeruli obtained) revealed a crescentic glomerulonephritis (Fig. 1). Specifically, 3 glomeruli exhibited global cellular crescents filling Bowman’s space, and 7 glomeruli had segmental cellular crescents; many glomerular capillary loops were collapsed or obliterated by fibrin and inflammatory cells, and foci of fibrinoid necrosis were present. Only 2 glomeruli were uninvolved. There was moderate interstitial edema with mild inflammatory infiltrate, but no significant chronic fibrosis or tubular atrophy, given the acute nature. Immunofluorescence microscopy demonstrated the defining feature of anti-GBM disease: strong linear deposition of IgG along the GBMs (on the capillary loops of all glomeruli). Complement component C3c and light chains were also positively stained in a linear pattern along the capillaries, although IgA and IgM showed no significant granular deposits. No obvious electron-dense deposits were seen on electron microscopy; however, the GBM appeared irregularly thickened in areas with crescents, and there was extensive foot process effacement from the severe injury. These findings confirmed the diagnosis of anti-GBM antibody glomerulonephritis.

Fig. 1.

Light microscopy (a–d), immunofluorescence (e–n), and electron microscopy (o, p) findings. The renal biopsy shows diffuse necrotizing crescentic glomerulonephritis with the hallmark linear IgG deposition along GBM and corresponding ultrastructural changes. a Hematoxylin and eosin (H&E) stain of a glomerulus reveals a large circumferential cellular crescent filling Bowman’s space and compressing the glomerular tuft, accompanied by segmental fibrinoid necrosis of the capillary tuft. b Periodic acid-Schiff (PAS) stain highlights the GBM (magenta) and shows collapsed capillary loops beneath an extensive cellular crescent, with segmental capillary wall destruction at the site of necrosis. c Periodic acid-Schiff methenamine (PASM) silver stain outlines the GBM in black and demonstrates a focal rupture of the GBM at the necrotic segment. d Masson’s trichrome stain depicts a circumferential fibrocellular crescent (blue collagen matrix) around the glomerulus and bright red fibrin in areas of active necrosis. e Direct immunofluorescence for IgG reveals strong linear capillary wall staining along the GBM – the classic “linear IgG” pattern diagnostic of anti-GBM nephritis. f–g IgG sub-class-specific immunofluorescence demonstrates that the deposits are polyclonal: IgG1 (f) and IgG2 (g) show intense linear GBM staining, whereas IgG3 and IgG4 are less intense. h, i Immunofluorescence for IgM (h) and IgA (i) showed no significant staining. j, k Kappa (j) and lambda (k) light chain stains show identical linear GBM staining. l Immunofluorescence for C1q is negative to faint, without a linear pattern. m Immunofluorescence for C3c demonstrates bright, linear staining along the glomerular basement membrane, colocalizing with IgG deposits. n Fibrinogen IF highlights abundant fibrin in the crescent and necrotic tuft (bright staining in Bowman’s space and capillary lumina). o, p Transmission electron microscopy demonstrates diffuse podocyte foot process effacement and irregular thickening of the glomerular basement membrane, without immune-type electron-dense deposits. These ultrastructural findings support the diagnosis of anti-GBM disease and distinguish it from immune complex-mediated glomerulonephritis.

Treatment and Course

Following the biopsy diagnosis, we intensified therapy. High-dose prednisone (60 mg PO daily) was continued. Given the severity of renal involvement (>80% crescents) and the patient’s young age, we decided to pursue every effort to recover kidney function. The patient was started on hemodialysis on hospital day 1 for symptomatic uremia, but immunosuppressive treatment was not abandoned. We performed additional plasma exchanges – two sessions of double-filtration plasmapheresis over the next week – to further remove circulating antibodies. Because of the suboptimal response to initial cyclophosphamide and concern for its cumulative toxicity, we opted to administer obinutuzumab as adjunct therapy. He received an infusion of obinutuzumab (500 mg IV on hospital day 9) to deplete B cells and halt ongoing anti-GBM antibody production. Over the subsequent weeks, the patient’s condition stabilized. His urine output remained adequate (no oligo-anuria), and by 2 weeks, the hematuria macroscopically improved (though microscopic hematuria persisted). Peripheral B-cell depletion was monitored by measuring circulating CD19⁺ lymphocyte counts. Within 2 weeks after administration of obinutuzumab, peripheral CD19⁺ B cells became nearly undetectable. The anti-GBM antibody titer became undetectable by 1 month of therapy. He required intermittent dialysis during the acute phase, but after approximately 1 month, his intrinsic renal function began to recover sufficiently that dialysis was no longer needed. By 3 months after presentation, his serum creatinine improved to ∼310 μmol/L (∼3.5 mg/dL), and he was independent of dialysis. Proteinuria had reduced to about 1+ on dipstick (sub-nephrotic), and the gross hematuria had resolved (only microscopic RBCs remained). Suppression of circulating B cells was maintained at 3 months. He tapered off prednisone over about 6 months. At the last follow-up (5 months after presentation), the patient was doing well clinically – he had returned to university classes – with a creatinine of 2.1–2.5 mg/dL (indicating CKD Stage 3) and no recurrence of anti-GBM antibodies. He did not experience any pulmonary complications throughout the course. The outcome in this case was a partial renal recovery: the patient sustained significant CKD but avoided permanent dialysis dependence, which is a relatively favorable result given the initial severity.

Discussion

This case illustrates a classic presentation of anti-GBM glomerulonephritis, while also introducing the novel therapeutic application of obinutuzumab in this rare but aggressive autoimmune disease. Traditionally, treatment consists of plasmapheresis, corticosteroids, and cyclophosphamide; however, many patients – especially those presenting with advanced renal injury – fail to recover kidney function. In this context, obinutuzumab, a type II glycoengineered anti-CD20 monoclonal antibody, offers an enhanced ability to deplete B cells and suppress pathogenic autoantibody production compared to first-generation agents like rituximab. Its use in our patient was associated with rapid anti-GBM antibody clearance and partial renal recovery, suggesting that more potent B-cell depletion strategies may hold promise in refractory or high-risk cases. Although data on obinutuzumab in anti-GBM disease are still limited, this case supports its further evaluation as part of aggressive multimodal therapy in selected patients.

The patient was a previously healthy young male who developed an acute febrile illness followed by gross hematuria and rapidly progressive renal failure. The temporal association with a dental extraction and subsequent infection raises the question of a triggering event. While most cases of anti-GBM disease are idiopathic, it is postulated that environmental factors can precipitate the autoimmune process in susceptible individuals [7]. Infections (such as upper respiratory viral infections) have been implicated as potential triggers in Goodpasture’s syndrome, possibly by inducing inflammation or exposing hidden antigens on alveolar or GBMs [8]. In this patient, the localized infection and inflammation following dental surgery might have led to enhanced exposure of alveolar basement membrane antigens or a nonspecific stimulation of the immune system, eventually prompting anti-GBM antibody formation. However, it should be noted that this link is speculative; no direct causative pathogen was identified in our case.

The hallmark of anti-GBM disease is the presence of autoantibodies targeting the GBM, and the definitive diagnosis is established either by serologic testing or kidney biopsy. In our case, the diagnosis was strongly supported by a positive anti-GBM antibody test in serum and was confirmed by kidney biopsy showing linear IgG deposits along the GBM. This immunofluorescent linear staining is a defining feature that distinguishes anti-GBM GN from other types of crescentic glomerulonephritides [5]. For instance, pauci-immune (ANCA-associated) GN typically has little or no immunoglobulin deposition, while immune-complex GN (such as lupus nephritis or IgA nephropathy) shows granular deposits on immunofluorescence. In anti-GBM disease, the deposits are uniformly distributed along the basement membrane, reflecting the binding of circulating anti-GBM IgG to the intrinsic collagen antigen [9]. In our patient, immunofluorescence was positive for linear IgG and C3, consistent with complement activation by the bound antibodies. Notably, no significant IgA or IgM deposits were seen, indicating the absence of coincident immune-complex glomerulonephritis. Our patient’s biopsy showed a majority of glomeruli with cellular crescents, confirming an advanced RPGN lesion. This pathologic severity correlated with his advanced renal dysfunction on presentation.

Despite the fulminant course, our patient had no pulmonary hemorrhage, which occurs in about 40–60% of classic Goodpasture’s syndrome cases [1]. The absence of lung involvement (sometimes termed “renal-limited” anti-GBM disease) is not uncommon, especially in patients who are non-smokers. Smoking and other lung injuries can enhance alveolar basement membrane antigen exposure, thereby precipitating lung hemorrhage in susceptible individuals; fortunately, this patient did not have those risk factors. The outcome in isolated renal anti-GBM disease is primarily determined by the extent of kidney damage at presentation. Prognostic factors include the level of serum creatinine (particularly if > 500–600 μmol/L), the presence of oliguria, and the percentage of glomeruli with crescents on biopsy. Unfortunately, our patient had 2 poor prognostic indicators (creatinine ∼700+ μmol/L and ∼83% of glomeruli with crescents). Historically, once patients require dialysis at presentation, the likelihood of renal recovery is very low – studies have shown that 80–100% of such patient’s progress to end-stage kidney disease despite therapy [3]. Indeed, older series reported renal survival rates of only around 10% in those who started dialysis [10]. More recent cohorts still find that dialysis dependence and >50% crescents predict extremely poor renal outcomes [5]. Our patient’s course, therefore, is somewhat atypical in that he regained enough kidney function to discontinue dialysis. This favorable partial recovery can likely be attributed to the prompt and aggressive treatment he received, and perhaps the fact that a minority of glomeruli were still intact (giving some chance for recovery). It underscores that even in “critical” cases, therapy may rescue some renal function, especially in a young patient – a point also noted in some case series where a small fraction of dialysis-presenting patients recover renal function with treatment.

The standard treatment for anti-GBM disease remains a combination of plasma exchange, corticosteroids, and cyclophosphamide [8]. Plasmapheresis is used daily or nearly daily for 2–3 weeks to remove circulating autoantibodies, while cyclophosphamide (an alkylating agent) and high-dose steroids act to suppress new antibody production and quell the immune-mediated inflammation [8]. Our patient received this standard of care promptly. Nevertheless, as in many severe cases, the renal injury had already advanced. Contemporary guidelines (KDIGO) even suggest that patients who present dialysis-dependent with 100% crescents and no pulmonary hemorrhage are unlikely to recover and might not benefit from aggressive immunosuppression [8]. However, given our patient’s young age and the fact that his crescents were not truly 100%, we pursued therapy to maximize any chance of renal recovery. We also added obinutuzumab, a monoclonal anti-CD20 antibody, after observing inadequate response to cyclophosphamide in the first 1–2 weeks. Obinutuzumab is not part of first-line therapy for anti-GBM disease, but there is growing interest in its use, especially if cyclophosphamide is contraindicated or ineffective [11]. B-cell depletion with obinutuzumab can theoretically halt autoantibody production at the source. Some case reports and small series have shown that obinutuzumab can help reduce anti-GBM antibody levels and treat pulmonary hemorrhage [12], but improvement in renal outcomes has been inconsistent. In our patient, we cannot be certain that obinutuzumab made the difference, but his anti-GBM titers did rapidly become negative, and he avoided permanent dialysis, so it may have contributed. Obinutuzumab was well-tolerated in this case, and no major infections occurred during therapy.

Recent advances in anti-GBM therapy include imlifidase, a recombinant cysteine protease that rapidly cleaves circulating IgG antibodies by targeting the hinge region [13]. This allows for near-immediate reduction in pathogenic anti-GBM antibodies and may be particularly useful in fulminant cases, especially those complicated by ANCA-positive antibodies [14]. However, imlifidase does not suppress ongoing antibody production as it does not target B cells [15]. In contrast, obinutuzumab provides more sustained immunologic control through CD20-positive B-cell depletion, thereby reducing autoantibody generation. These therapies represent mechanistically distinct approaches – immediate antibody removal versus suppression of antibody production – and may have complementary roles when used in combination in selected clinical settings.

In conclusion, this case highlights the potential of obinutuzumab as a promising therapeutic option in anti-GBM disease. The addition of obinutuzumab, offers a novel approach to more effectively suppress antibody production. These findings suggest that early and aggressive B-cell-targeted therapy with obinutuzumab may improve outcomes in selected patients with anti-GBM glomerulonephritis and warrants further clinical investigation.

Statement of Ethics

This study was performed in accordance with the Declaration of Helsinki. Ethics approval for this human study was waived by the Ethics Committee of Changzheng Hospital. All adult participants provided written informed consent to participate in this study. Written informed consent was obtained from the individuals for publication of the details of their medical case and any accompanying images.

Conflict of Interest Statement

The authors declare no competing interests.

Funding Sources

The study was funded by Shanghai Science and Technology Innovation Action Plan of Scientific Instruments and Chemical Reagents Project (24142201800) and China Scholarship Council (202408310237). The funder had no role in the design, data collection, data analysis, and reporting of this study.

Author Contributions

C.X. and B.Y. contributed to the conception and design of the report and drafted the initial manuscript. Y.Q. and Y.L. collected and analyzed the clinical data. X.L. and N.L. performed the pathological evaluation and prepared the images. X.H. and Y.Q. assisted with the literature review and discussion. N.L. and J.W. critically revised the manuscript for important intellectual content. All authors read and approved the final manuscript.

Funding Statement

The study was funded by Shanghai Science and Technology Innovation Action Plan of Scientific Instruments and Chemical Reagents Project (24142201800) and China Scholarship Council (202408310237). The funder had no role in the design, data collection, data analysis, and reporting of this study.

Data Availability Statement

All data generated during this study are included in this article. Further inquiries can be directed to the corresponding author.