RCD2 / Perrigo Company - LARVOL DELTA

Beyond Gluten-Free: Recognizing RCD2 Before Malignant Transformation (ACG 2026) - "Clinicians should maintain a high index of suspicion for RCD2 in patients with celiac disease who have persistent symptoms despite a gluten-free diet to facilitate timely diagnosis and prevent progression to EATL. Figure: Edematous, erythematous, scalloped, and ulcerated mucosa within the proximal jejunum."

Celiac Disease • Crohn's disease • Gastroenterology • Hematological Malignancies • Immunology • Inflammatory Bowel Disease • Lymphoma • T Cell Non-Hodgkin Lymphoma • CRP

Beyond the Binary: A Case of Refractory Celiac Disease With Inconclusive T-Cell Receptor Testing and Evolving Clonality (ACG 2026) - "The patient has since shown moderate improvement on prednisone, azathioprine, and infliximab. In similarly ambiguous cases, serial TCR testing should be considered to monitor for evolving clonality and guide management. Figure: Figure legend: A. Hematoxylin and Eosin staining shows mild increase in intraepithelial lymphocytes (IELs) with mild villous blunting (10X magnification) B. Higher magnification (20X) from the yellow boxed area of part A showing mostly of small mature lymphocytes without significant atypia (yellow arrows) C. CD3 stain (20X) showing increased IELs, CD20 (inset) shows no B cells D. CD8 stain (20X) showing positivity in these T cells E. CD4 stain (20X) is not expressed in the IELs F. CD5 stain (20X) showing no expression of CD5 in these cells G. CD2 stain (20X) showing partial loss of CD2 (CD8>CD2) in these cells H. CD56 stain (20X) showing no expression in these cells Figure: Endoscopic image showing mild edematous and scalloped mucosa throughout..."

Clinical • IO biomarker • Atrial Fibrillation • Cardiovascular • Celiac Disease • Hematological Malignancies • Immunology • Lymphoma • CD2 • CD20 • CD4 • CD5 • CD8 • NCAM1

A Multi-omics Regulated Cell Death Framework Defines Immune Phenotypes and Guides Precision Therapy in Colorectal Cancer. (PubMed, Transl Oncol) - "Dasatinib was prioritized for immune-cold, high-risk tumors, with preliminary evidence supporting its activity in CRC cells, while functional assays suggested a role for FSTL3 in growth, invasion, epithelial-mesenchymal transition, and apoptosis regulation. These findings suggest that RCD-based multi-omics analysis may refine CRC stratification and help generate therapeutic hypotheses."

IO biomarker • Journal • Tumor mutational burden • Colorectal Cancer • Oncology • Solid Tumor • TMB

Enteropathy-associated T-cell lymphoma: molecular clonal evolution and its clinical consequences. (PubMed, Haematologica) - "EATL develops via parallel subclonal evolution and selection from a pool of locally residing jejunal Tcell populations with a restricted TR repertoire and a heterogeneous genetic makeup, but not necessarily from RCD populations in the duodenum. These findings provide leads for modifying current clinical decision-making for RCD and EATL patients."

IO biomarker • Journal • Celiac Disease • Hematological Malignancies • Immunology • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

Gluten Catastrophe: A Fatal Case of Refractory Celiac Disease Type 2. (PubMed, ACG Case Rep J) - "He ultimately elected for palliative care and died. This case highlights the diagnostic challenges, morbidity, and high mortality associated with RCD2."

Journal • Celiac Disease • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Immunology • Infectious Disease • Lymphoma • Oncology • Pain • Palliative care • Pneumonia • Respiratory Diseases • Septic Shock

CLONAL LYMPHOCYTE EXPANSIONS AND JAK-STAT PATHWAY MUTATIONS DEFINE A PATHOGENIC CONTINUUM DRIVING RESISTANCE TO GLUTEN-FREE DIET IN CELIAC DISEASE. (PubMed, Gastroenterology) - "These findings suggest that RCD subtypes may share underlying mechanisms driven by clonal evolution and JAK-STAT dysregulation. They also highlight the potential limitations of JAK inhibitor monotherapy and the importance of molecularly informed therapeutic strategies."

Journal • Celiac Disease • Hematological Malignancies • Immunology • Lymphoma • Oncology • CD4 • STAT3

Timing of Lymphoproliferative Disorder Diagnosis in Patients With Celiac Disease (ACG 2025) - "There were 87 cases of LPD identified in 82 patients, with four patients developing more than one LPD. There were 41 cases of T-cell NHL, with 90% presenting concurrently or after CeD diagnosis. The four cases presenting before CeD diagnosis were cutaneous: cutaneous anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, cutaneous T-cell lymphoma (two cases), and lymphomatoid papulosis type A. There were 36 cases of B-cell NHL, with 31% presenting before and 69% presenting concurrently or after CeD diagnosis.Comparing patients diagnosed with LPD before CeD diagnosis to those diagnosed concurrently or after CeD diagnosis, we found a mean age of CeD diagnosis of 58.6 and 57.6 years (p = 0.9), respectively, and a mean age of LPD diagnosis of 48.5 and 65.5 years (p < 0.001), respectively."

Clinical • Celiac Disease • Cutaneous T-cell Lymphoma • Hodgkin Lymphoma • Immunology • Multiple Myeloma • Non-Hodgkin’s Lymphoma • T Cell Non-Hodgkin Lymphoma • ALK

Imported Malaria and Local Transmission Hotspots in Zanzibar: Findings from Reactive Case Detection (ASTMH 2025) - "While resurgence in 2023 was most marked in urban Mjini, residence in a rural area remained a significant factor (OR = 1.6, 95% CI: 1.2-2.1). Extending RCD to potentially capture late secondary cases was a worthwhile strategy that uncovered more cases in the RDT-positive range."

Clinical • Late-breaking abstract • Infectious Disease • Malaria

Expanded T cell clones with lymphoma driver somatic mutations accumulate in refractory celiac disease. (PubMed, Sci Transl Med) - "Furthermore, the mutant T cells formed large TCRαβ clones and displayed inflammatory and cytotoxic molecular profiles. Thus, accumulation of lymphoma driver-mutated T cells and sCD3- progenitors may contribute to chronic, nonresponsive celiac disease."

Journal • Celiac Disease • Hematological Malignancies • Immunology • Inflammatory Bowel Disease • Lymphoma • Oncology

Endoscopic Diagnosis and Management of a Rare Case of T-Cell Associated Enteropathy (ACG 2024) - "While initial biopsies were inconclusive of both celiac disease and lymphoma, obtaining additional biopsies and sending them for expert GI pathological review expedited diagnosis and management of this patient. Figure: T-cell associated enteropathy"

Clinical • Anemia • Celiac Disease • Hematological Disorders • Hematological Malignancies • Immunology • Inflammatory Bowel Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pain • T Cell Non-Hodgkin Lymphoma

Refractory Celiac Crisis: Rare and Life Threatening Presentation of Hypovolemic Shock in Adult Onset Celiac Disease (ACG 2024) - "Our case demonstrates that refractory CC may indicate alternative underlying pathology such as RCD2 and may require different therapeutic decisions. Figure: Atrophic appearing duodenal mucosa with notching consistent with celiac disease"

Clinical • Celiac Disease • Diabetes • Hematological Malignancies • Immunology • Infectious Disease • Lymphoma • Metabolic Disorders • Oncology • Peptic Ulcer • Type 2 Diabetes Mellitus

Prevalence and Etiologies of Non-Responsive Celiac Disease: A Systematic Review and Meta-analysis (ACG 2023) - "Of a total of 792 search results, after inclusion and exclusion criteria, 8 studies were included in the systematic review, of which 5 studies (n= 4,414) reported data on the prevalence of NRCD and 6 studies (n= 678) reported the causes of NRCD. Pooled prevalence of NRCD was 22% (95%CI, 11-35%, I 2 = 98.6%, figure 1). Amongst patients with NRCD, inadvertent exposure to gluten was the most common cause (49% [95%CI, 36-63%, I 2 = 86.7%]), followed by functional gastrointestinal disorders including irritable bowel syndrome (21% [95%CI, 13-30%, I 2 = 81.7%]) and RCD1 (10% [95%CI, 0-33%, I 2 = 96.4%])."

Retrospective data • Review • Celiac Disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease

BUDESONIDE INDUCES FAVOURABLE HISTOLOGIC AND SYMPTOMATIC RECOVERY IN PATIENTS WITH NON-RESPONSIVE AND REFRACTORY COELIAC DISEASE WHEN GIVEN IN AN OPEN CAPSULE FORMAT (UEGW 2023) - "OCB was well tolerated and associated with improvements in enteropathy in 81% and symptoms in 89% of NRCD and RCD patients in contrast to lower rates with CCB. Prospective studies are warranted to confirm the efficacy and long-term safety of budesonide delivered to the proximal small bowel in patients with NRCD and RCD."

Clinical • Candidiasis • Celiac Disease • CNS Disorders • Diabetes • Gastroenterology • Immunology • Insomnia • Movement Disorders • Sleep Disorder

Long Term Follow up after Adoptive Transfer of CD19-Specific CAR+ T Cells Genetically Modified Via Non-Viral Sleeping Beauty System Following Hematopoietic Stem Cell Transplantation (HSCT) (ASH 2017) - P1,P=N/A; "...T cells were genetically modified using DNA plasmids from the SB platform to stably express CD19RCD28 and selectively propagated ex vivo with activating and propagating cells (AaPC) with cytokines...These encouraging results support further clinical development of this non-viral gene therapy approach. Figure: Overall and progression-free survivals of recipients of SB-modified CAR+ T cells after autologous and allogeneic HSCT."

Acute Lymphocytic Leukemia • Biosimilar • Graft versus Host Disease • Non-Hodgkin’s Lymphoma

Shortening the Time to Manufacture CAR+ T Cells with Sleeping Beauty System Supports T-Cell Engraftment and Anti-Tumor Effects in Patients with Refractory CD19+ Tumors (ASH 2017) - P1; "...This CAR (CD19RCD28) used a Fc-based extracellular stalk and T cells were generated after 28 days (4 “stimulations”) of recursive culture on activating and propagating cells (AaPC)... These initial data describing the infusion of SB-modified T cells with a revised extracellular domain and under reduced manufacturing time results in the detection of genetically modified T cells and anti-tumor effects in patients with relapsed/refractory ALL apparently without clinically-significant CRS. These data support advancing an approach for non-viral gene transfer to administer CAR+ T cells, and working toward even shorter manufacturing times.nFigure: Persistence of circulating CD19-specific CAR+ T cells in patients after single infusion of SB-modified T cells, as determined by ddPCR."

Adverse events • Biosimilar • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Graft versus Host Disease • Indolent Lymphoma

TREATMENT OF REFRACTORY CELIAC DISEASE TYPE 1 WITH VEDOLIZUMAB - PRESENTATION OF TWO CASES (UEGW 2022) - "No drug treatment is well documented. Two patients with RCD1 that had failed treatment with budesonide and infliximab were successfully off-label treated with vedolizumab, an anti-integrin monoclonal antibody against alpha4beta7. Case 1 a female born 92...Some clinical effect of infliximab, developed infusion reactions, did not tolerate adalimumab... These case reports are the first descriptions of effects of the anti-integrin Mab vedolizumab. A trial with an oral antagonist is ongoing. The rationale is supported by these two cases."

Clinical • Celiac Disease • Dermatology • Diabetes • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Metabolic Disorders • Psoriasis • Retinal Disorders • Type 1 Diabetes Mellitus

REFRACTORY TYPE 2 CELIAC DISEASE AND ASSOCIATED CIRCULATING MICRORNAS: NETWORKS WITH BIOLOGICAL FUNCTIONS (UEGW 2022) - " As expected, the identified miRNAs are associated with an increase in inflammation, while others represent signal progression of the pathology that are also closely linked to oncogenesis. Interestingly, some deregulated miRNAs could reflect altered conditions derived from both epigenetic and post-transcription modifications."

Celiac Disease • Hematological Malignancies • Immunology • Inflammation • Lymphoma • Oncology • MIR122 • MIR181B1 • MIR490

Non-Responsive and Refractory Coeliac Disease: Experience from the NHS England National Centre. (PubMed, Nutrients) - "The contemporary mortality data in RCD2 remains poor; patients with suspected RCD2 should be referred to a recognised national centre for consideration of novel therapies. The high frequency of urinary GIP positivity suggests that gluten exposure may be common in RCD1; further studies with matched controls are warranted to assess this further."

Journal • Celiac Disease • Immunology • Inflammation • Mucositis

Presence of Clonal T-cell Receptor Gene Rearrangement is Specific for Refractory Celiac Disease Type 2 (USCAP 2022) - "Our study showed clonal TCRGR detected in our clinical laboratory is quite sensitive (90%) and specific (96.3%) for RCD2 and can be reliably used to detect clonal T-cell populations of IELs in patients with RCD. Discrepancy between the current and previous studies regarding its specificity might be due to difference in regions of TCR gene covered and interobserver variability."

IO biomarker • Celiac Disease • Gastrointestinal Disorder • Immunology • CD8

Hemophagocytic Lymphohistiocytosis as a Complication of Refractory Celiac Disease Type II That Transforms into a T-cell Lymphoma: A Case Report (ACG 2021) - "His RCD was treated with prednisone and subsequently with budesonide starting at 9 mg triple-phase release method, and then at 3 mg twice a day...He received treatment for HLH and EATL with high-dose steroids and etoposide before starting treatment with BV-CHP (Brentuximab Vedotin, cyclophosphamide, doxorubicin, prednisone) for T-cell lymphoma. The prognosis of RCD2 is often poor and can lead to full-blown transformation to EATL. HLH is a severe inflammatory and immune-mediated disease that can be associated with CD and EATL and prompt diagnosis is essential in preventing fatal outcomes."

Clinical • Celiac Disease • Fatigue • Gastrointestinal Disorder • Hematological Malignancies • Hepatology • Immunology • Lymphoma • Oncology • Pain • Rare Diseases • T Cell Non-Hodgkin Lymphoma • TNFRSF8

Single-Cell Measurements of Two-Dimensional Binding Affinity Across Cell Contacts. (PubMed, Biophys J) - "In summary, this method not only allows for single-cell affinities to be measured, but it can also reduce measurement and analysis time and improve measurement accuracy. Due to the low spread in 2D K within the cell population, the analysis can further be restricted to the cells showing the strongest binding, paving the way for using this method to study weak binding events."

Journal • CD2

Characterization of a novel allele encoding pheophorbide a oxygenase in rice. (PubMed, Plant Signal Behav) - "Furthermore, the level of chlorophyllide a, the product of chlorophyllase, increased significantly, indicating chlorophyllase might play a role in chlorophyll degradation in rice. Our results suggested that the I576F substitution disrupted PAO function, leading to O accumulation and chlorophyll degradation breakdown in rice."

Journal

[VIRTUAL] REDEFINING THE DIAGNOSIS OF TYPE 1 REFRACTORY COELIAC DISEASE USING URINE GLUTEN IMMUNOGENIC PEPTIDES (UEGW 2020) - "From the RCD1 cohort, 22 patients (33.3%) were successfully treated with budesonide, with 44 patients (66.7%) having ongoing VA. A high proportion of individuals with RCD1 appear to have ongoing gluten exposure despite reported strict GFD adherence, as assessed by urine GIP. Urine GIP may re-define and enable the accurate diagnosis of RCD1 in the future."

Celiac Disease • Immunology

Deregulation of miRNAs-cMYC circuits is a key event in refractory celiac disease type-2 lymphomagenesis. (PubMed, Clin Sci (Lond)) - "Our data suggest that a miRNAs circuit supports activation of STAT3 and c-Myc oncogenic signaling in RCD2, thus contributing to lymphomagenesis. This novel understanding might pave the way to personalized medicine approaches for RCD and EATL."

Journal • Celiac Disease • Hematological Malignancies • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma