High-throughput sequencing of IgH gene in minor salivary glands from Sjögren's syndrome patients reveals dynamic B cell recirculation between ectopic lymphoid structures

Carlotti, Emanuela; Murray-Brown, William; Blighe, Kevin; Caliste, Mattia; Astorri, Elisa; Sutcliffe, Nurhan; Tappuni, Anwar R.; Pitzalis, Costantino; Corsiero, Elisa; Bombardieri, Michèle

doi:10.55563/clinexprheumatol/82u3cs

Cited by 3 publications

(3 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This approach is essential in DLBCL treatment but not always necessary in MALT lymphoma, given its non-complete response to Rituximab. Indeed, as recently demonstrated, B-cells are able to recirculation and independently proliferate in SGs and the BAFF-rich prostimulatory salivary microenvironment secondary to an indiscriminate B-cell depletion may lead to an incomplete elimination of the neoplastic clone or to selection of other clones (70,71). Management of SS lymphoma still represents an unmet need.…”

Section: Outcome and Management Of Ss-related Lymphoma: What Have We ...mentioning

confidence: 99%

“…• Prevalence of different lymphoma isotypes has been deeply characterised in two wide multicentre SS cohorts (62,63). • Lymphoepithelial lesions, peculiar oncogenic events and B cell hyperactivation have been demonstrated to exert a central role in lymphoma pathogenesis (68)(69)(70)(71)(72). • Parotid salivary swelling has been identified as early predictor of lymphoma in SS (74).…”

Section: Take Home Messagesmentioning

confidence: 99%

See 1 more Smart Citation

Sjögren's syndrome: one year in review 2023

Longhino,

Chatzis,

Dal Pozzolo

et al. 2023

Clinical and Experimental Rheumatology

View full text Add to dashboard Cite

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder characterised by the T-cell-mediated hyperactivation of B-cells and cytokine production. The condition may evolve from an asymptomatic, indolent course, with glandular involvement, to extraglandular systemic manifestations up to lymphoma development. On tissue level, the typical feature is the lymphocytic infiltration of the salivary gland by B-, T-and antigen presenting cells, as mirrored by the diagnostic cornerstone role of minor salivary gland (MSG) biopsy. Recently, increasing research focused on the investigation of mechanisms underlying the complex pathogenesis of the disease and highlighted the multifactorial nature of SS consisting of concomitant involvement of environmental, genetic, neuroendocrine and immune factors. In particular, many aspects have been investigated regarding genetic and epigenetics, the role of specific B-and T-cell phenotypes and the investigation of disease-specific biomarkers as predictors of disease development, activity, and lymphomagenesis. Surely, a deeper understanding of these multiple mechanisms may facilitate earlier diagnosis, enable subphenotyping of patients and open novel therapeutic possibilities to address the unmet needs of the disease in the upcoming years.In this review, following the others of this series, we will summarise the most recent literature on pSS pathogenesis and clinical features focusing in particular on new insights into pSS molecular stratification and therapeutic advances in the era of precision medicine.

show abstract

Section: Outcome and Management Of Ss-related Lymphoma: What Have We ...mentioning

confidence: 99%

Section: Take Home Messagesmentioning

confidence: 99%

Sjögren's syndrome: one year in review 2023

Longhino,

Chatzis,

Dal Pozzolo

et al. 2023

Clinical and Experimental Rheumatology

View full text Add to dashboard Cite

show abstract

“…This new technique allows the identification of genes that encode key proteins [ 115 ], i.e., genes that are engaged or necessary for cellular physiology and survival. Its capacity to edit the panorama of cellular reactions to desiccation challenge has led to new insights into the pathophysiology of, especially, Sjögren’s Syndrome [ 116 , 117 , 118 , 119 , 120 , 121 ], although the application of this technique to the cornea and ocular surface is yet very limited [ 122 ].…”

Section: Stress Stress Factors and Stress Tolerancementioning

confidence: 99%

Ocular Surface Allostasis—When Homeostasis Is Lost: Challenging Coping Potential, Stress Tolerance, and Resilience

Setten

2023

Biomolecules

View full text Add to dashboard Cite

The loss of ocular surface (OS) homeostasis characterizes the onset of dry eye disease. Resilience defines the ability to withstand this threat, reflecting the ability of the ocular surface to cope with and bounce back after challenging events. The coping capacity of the OS defines the ability to successfully manage cellular stress. Cellular stress, which is central to the outcome of the pathophysiology of dry eye disease, is characterized by intensity, continuity, and receptivity, which lead to the loss of homeostasis, resulting in a phase of autocatalytic dysregulation, an event that is not well-defined. To better define this event, here, we present a model providing a potential approach when homeostasis is challenged and the coping capacities have reached their limits, resulting in the stage of heterostasis, in which the dysregulated cellular stress mechanisms take over, leading to dry eye disease. The main feature of the proposed model is the concept that, prior to the initiation of the events leading to cellular stress, there is a period of intense activation of all available coping mechanisms preventing the imminent dysregulation of ocular surface homeostasis. When the remaining coping mechanisms and resilience potential have been maximally exploited and have, finally, been exceeded, there will be a transition to manifest disease with all the well-known signs and symptoms, with a shift to allostasis, reflecting the establishment of another state of balance. The intention of this review was to show that it is possibly the phase of heterostasis preceding the establishment of allostasis that offers a better chance for therapeutic intervention and optimized recovery. Once allostasis has been established, as a new steady-state of balance at a higher level of constant cell stress and inflammation, treatment may be far more difficult, and the potential for reversal is drastically decreased. Homeostasis, once lost, can possibly not be fully recovered. The processes established during heterostasis and allostasis require different approaches and treatments for their control, indicating that the current treatment options for homeostasis need to be adapted to a more-demanding situation. The loss of homeostasis necessarily implies the establishment of a new balance; here, we refer to such a state as allostasis.

show abstract