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Such a detailed summary is worth collecting! Co-sponsored by the National Clinical Research Center for Skin and Immune Diseases (NCRC-DID), China Rheumatism and Immunology Medical Association (CRCA), National Rheumatism Data Center (CRDC), and China Systemic Lupus Erythematosus Research Collaboration Group (CSTAR) The "First National Clinical Research Center for Skin and Immune Diseases Annual Conference and CSTAR/CRDC/CRCA Annual Conference" has successfully concluded.
At the meeting, Professor Fei Yunyun from the Department of Rheumatology and Immunology of Peking Union Medical College Hospital introduced the annual progress of Sjogren's syndrome (pSS).
Professor Fei Yunyun introduced that pSS is a systemic disease.
In addition to gland involvement, there will be many extra-glandular manifestations, such as systemic lymphadenopathy, kidney involvement, central nervous system, lungs, joints, skin, Muscle and peripheral neuropathy, etc.
01 The pathogenesis of pSS has made certain progress in genetic research in recent years, emphasizing many risk alleles of pSS, some of which overlap with other autoimmune diseases.
Therefore, it is expected that these data can be used to help stratify patients for early diagnosis of the disease and treatment plan.
In terms of epigenetic mechanisms, mechanisms such as DNA methylation, miRNA, and lncRNA help to start and close the expression of genes related to inflammation pathways, and may become targets for improving pSS therapy.
In terms of innate immunity, the pDC transcription profile of pSS patients has been explored, which is related to the promotion of cytokine production by pDCs.
Some evidence supports the role of TLR7-led innate immunity in the development of pSS sialanditis.
In terms of adaptive immunity, the high expression of epithelial matrix interacting protein 1 (EPSTI1) in B cells of patients with pSS promotes the abnormal activation of B cells.
EPSTI1 may be involved in the pathogenesis of pSS and is a potential therapeutic target of pSS.02 Clinical manifestations 1 PSS patients with glandular symptoms have more severe dry eye symptoms compared with non-SS dry eye subjects.
Anti-salivary protein 1 (SP1), anti-carbonic anhydrase 6 (CA6), and anti-parotid secretory protein (PSP) are considered to be markers for early identification of pSS patients, which may be related to the occurrence of dry eye in these patients.
Anti-CA6 antibodies are significantly correlated with corneal and conjunctival staining scores, and are associated with severe dry eye.
The prevalence of dental caries in patients with pSS is higher, possibly not only because of reduced saliva, but also because of changes in oral microbiology.
In pSS patients and other subjects with reduced saliva function, there is a link between low saliva flow rate and increased risk of dental caries.
A recent retrospective study compared caries risk factors in non-SS patients with reduced saliva function and pSS patients.
Compared with other groups, the total number of caries in the pSS group was significantly increased.
The salivary microbiota of pSS is significantly different from the non-pSS group.
The salivary microbiota of pSS has a lower abundance of Neisseria and Porphyromonas and a higher abundance of Veyronella.
2 In addition to the cardiovascular involvement of glands, more than 1/4 patients may have systemic involvement, of which cardiovascular symptoms are the most common.
Compared with the general population (35-37 years old), pSS patients are characterized by an increased prevalence of subclinical atherosclerosis and a higher risk of cerebrovascular and cardiovascular events.
Traditional cardiovascular risk factors play a related role in the contribution of atherosclerotic damage in pSS patients.
Hypertension, as a prominent cardiovascular risk factor, is more common in pSS patients and is associated with an increased risk of overt cardiovascular events Related.
In a recent cohort study of 367 pSS patients, hypertension, old age, and extraglandular involvement were independently associated with cardiovascular events.
3 Compared with patients without lung disease, patients with pSS with lung involvement have a lower quality of life and higher mortality.
Airway involvement may lead to tracheal, bronchiolar, and pulmonary complications, including tracheobronchial mucosal sicca, bronchiolitis and bronchiectasis, lung cysts, and bronchial or lung-related lymphomas.
Interstitial lung disease (ILD) has been reported in 3%-11% of pSS patients.
Advanced age, Raynaud’s phenomenon, and esophageal involvement have been identified as predictors of poor prognosis for patients with pSS and ILD; elevated serum KL-6 levels are associated with higher mortality; lower forced vital capacity is significantly associated with advanced age and survival; Baseline anti-neutrophil cytoplasmic antibody (ANCA) peroxidase positive can predict the development of ILD in pSS.
4 Kidney involvement Kidney involvement may significantly affect the course of the disease.
Patients with pSS with renal damage have unique clinical features, high disease activity, high salivary gland biopsy positive rate, and increased inflammation, but the prevalence of dry eye is low.
Tubular interstitial nephritis (TIN): delayed disease course, no response to immunosuppressive therapy; glomerulonephritis (GN)/combined cryoglobulinemia: to immunosuppressive agents such as rituximab, mycophenolate mofetil It reacts well with cyclophosphamide.
α-1 microglobulin (α-1-MG) has been shown to be a useful biomarker of renal involvement in pSS.
Studies have shown that kidney involvement is related to increased levels of creatinine, cystatin C and α-1-MG.
5 Nerve involvement Peripheral nervous system (PNS) patients often show more active systemic diseases and lower features of Sjogren.
The performance is heterogeneous, the diagnosis is complicated, and the prognosis is poor.
PNS is significantly associated with high levels of disease activity.
Because it can be disabling, nerve involvement can have a negative impact on the quality of life of patients, and immunosuppressive therapy is often required.
PNS is most affected, especially small fiber neuropathy (SFN) and dorsal root ganglion disease, which are often described as special features; studies have shown that SFN patients are predominantly male, with anti-SSA/RO52/60 antibodies and rheumatoid factor (RF) The frequency of positivity is reduced; anti-SSA/RO-negative patients have a higher prevalence of PNS than positive patients.
6 Joint involvement Joint involvement is one of the most common manifestations of disease.
Among 20% to 60% of pSS patients, about 1/3 develop synovitis similar to rheumatoid arthritis (RA).
Compared with non-synovitis patients, patients with synovitis are characterized by swelling of the parotid glands and a higher frequency of swollen lymph nodes.
pSS-associated arthritis is usually non-invasive, and patients with anti-cyclic citrullinated peptide (CCP) antibodies are at higher risk of RA.
A study showed that anti-CCP antibodies were significantly related to the risk of arthritis and RA development in patients with pSS.
All pSS patients with anti-CCP antibodies did not observe the progress of structural erosion during follow-up; immunosuppressants include hydroxychloroquine and methotrexate Rituxan and rituximab show similarly good effects in reducing pain and joint inflammation.
7 Other autoimmune diseases Compared with the general population, patients with pSS are more likely to suffer from other autoimmune diseases, such as autoimmune thyroiditis and celiac disease.
Primary SS with Hashimoto's thyroiditis (HT) is characterized by a higher incidence of lymphatic structure lesions and urticaria, and anti-RO/SSA antibodies are more common in the pSS group.
Research suggests that young patients with pSS can be considered for CD screening when the disease is diagnosed.
8 Lymphoma The risk of B-cell lymphoma in patients with pSS is 15-20 times that of the general population, which is attributed to chronic B-cell activation in patients with pSS.
These lymphomas are multiple B-cell non-Hodgkin's lymphomas, which often occur in organs where pSS is active, such as the salivary glands.
It is recommended to perform the simplest tests every 1-2 years, such as lymphocyte count, protein electrophoresis, RF, C3 and C4 proteins, and cryoglobulin.
For higher-risk patients, it is recommended to evaluate every 6 months.
When lymphoma is suspected, imaging tests such as PET-CT may be helpful, and the diagnosis requires tissue biopsy.
03 Treatment 1 Fatigue symptoms There is currently no drug proven to be effective for the fatigue of pSS patients.
Non-pharmacological strategies may have potential benefits.
For example, supervised exercise and non-invasive vagus nerve stimulation have been shown to improve fatigue, cardiorespiratory health, and exercise tolerance.
2 The new formula of cyclosporine A (CyA) and sirolimus for the treatment of dry eyes may be superior in bioavailability and effectiveness.
The results of the study show that CyA cationic emulsion has a significant improvement effect on pSS patients with severe dry eye, but has no significant effect on the entire pSS population.
Compared with CyA, sirolimus is more effective, but has poor water solubility, which limits its ability to penetrate the tear film barrier.
3pSS-related lymphoma is currently undergoing multiple clinical trials to test the efficacy of different drugs targeting B cells and T cells.
Indolence: wait and see, cytotoxic therapy, low-dose radiotherapy, surgery, chemotherapy or chemotherapy; aggressiveness: RCHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone).
Biological agents can be used to treat borderline cases that are difficult to clearly diagnose as B-cell malignancies and the pre-lymphoma state of pSS.
A French study showed that about two-thirds of patients treated with rituximab showed systemic improvement, especially those with vasculitis or persistent/recurrent parotid swelling caused by cryoglobulinemia.
Abatacept, Ialiumab, and Ofatumumab may be effective for more severe clinical manifestations.
Finally, there are some new drugs for the excessive proliferation of B cells, including small molecule inhibitors, anti-IL-7 treatments, etc.
, which are in clinical trials and are worth looking forward to.
At the meeting, Professor Fei Yunyun from the Department of Rheumatology and Immunology of Peking Union Medical College Hospital introduced the annual progress of Sjogren's syndrome (pSS).
Professor Fei Yunyun introduced that pSS is a systemic disease.
In addition to gland involvement, there will be many extra-glandular manifestations, such as systemic lymphadenopathy, kidney involvement, central nervous system, lungs, joints, skin, Muscle and peripheral neuropathy, etc.
01 The pathogenesis of pSS has made certain progress in genetic research in recent years, emphasizing many risk alleles of pSS, some of which overlap with other autoimmune diseases.
Therefore, it is expected that these data can be used to help stratify patients for early diagnosis of the disease and treatment plan.
In terms of epigenetic mechanisms, mechanisms such as DNA methylation, miRNA, and lncRNA help to start and close the expression of genes related to inflammation pathways, and may become targets for improving pSS therapy.
In terms of innate immunity, the pDC transcription profile of pSS patients has been explored, which is related to the promotion of cytokine production by pDCs.
Some evidence supports the role of TLR7-led innate immunity in the development of pSS sialanditis.
In terms of adaptive immunity, the high expression of epithelial matrix interacting protein 1 (EPSTI1) in B cells of patients with pSS promotes the abnormal activation of B cells.
EPSTI1 may be involved in the pathogenesis of pSS and is a potential therapeutic target of pSS.02 Clinical manifestations 1 PSS patients with glandular symptoms have more severe dry eye symptoms compared with non-SS dry eye subjects.
Anti-salivary protein 1 (SP1), anti-carbonic anhydrase 6 (CA6), and anti-parotid secretory protein (PSP) are considered to be markers for early identification of pSS patients, which may be related to the occurrence of dry eye in these patients.
Anti-CA6 antibodies are significantly correlated with corneal and conjunctival staining scores, and are associated with severe dry eye.
The prevalence of dental caries in patients with pSS is higher, possibly not only because of reduced saliva, but also because of changes in oral microbiology.
In pSS patients and other subjects with reduced saliva function, there is a link between low saliva flow rate and increased risk of dental caries.
A recent retrospective study compared caries risk factors in non-SS patients with reduced saliva function and pSS patients.
Compared with other groups, the total number of caries in the pSS group was significantly increased.
The salivary microbiota of pSS is significantly different from the non-pSS group.
The salivary microbiota of pSS has a lower abundance of Neisseria and Porphyromonas and a higher abundance of Veyronella.
2 In addition to the cardiovascular involvement of glands, more than 1/4 patients may have systemic involvement, of which cardiovascular symptoms are the most common.
Compared with the general population (35-37 years old), pSS patients are characterized by an increased prevalence of subclinical atherosclerosis and a higher risk of cerebrovascular and cardiovascular events.
Traditional cardiovascular risk factors play a related role in the contribution of atherosclerotic damage in pSS patients.
Hypertension, as a prominent cardiovascular risk factor, is more common in pSS patients and is associated with an increased risk of overt cardiovascular events Related.
In a recent cohort study of 367 pSS patients, hypertension, old age, and extraglandular involvement were independently associated with cardiovascular events.
3 Compared with patients without lung disease, patients with pSS with lung involvement have a lower quality of life and higher mortality.
Airway involvement may lead to tracheal, bronchiolar, and pulmonary complications, including tracheobronchial mucosal sicca, bronchiolitis and bronchiectasis, lung cysts, and bronchial or lung-related lymphomas.
Interstitial lung disease (ILD) has been reported in 3%-11% of pSS patients.
Advanced age, Raynaud’s phenomenon, and esophageal involvement have been identified as predictors of poor prognosis for patients with pSS and ILD; elevated serum KL-6 levels are associated with higher mortality; lower forced vital capacity is significantly associated with advanced age and survival; Baseline anti-neutrophil cytoplasmic antibody (ANCA) peroxidase positive can predict the development of ILD in pSS.
4 Kidney involvement Kidney involvement may significantly affect the course of the disease.
Patients with pSS with renal damage have unique clinical features, high disease activity, high salivary gland biopsy positive rate, and increased inflammation, but the prevalence of dry eye is low.
Tubular interstitial nephritis (TIN): delayed disease course, no response to immunosuppressive therapy; glomerulonephritis (GN)/combined cryoglobulinemia: to immunosuppressive agents such as rituximab, mycophenolate mofetil It reacts well with cyclophosphamide.
α-1 microglobulin (α-1-MG) has been shown to be a useful biomarker of renal involvement in pSS.
Studies have shown that kidney involvement is related to increased levels of creatinine, cystatin C and α-1-MG.
5 Nerve involvement Peripheral nervous system (PNS) patients often show more active systemic diseases and lower features of Sjogren.
The performance is heterogeneous, the diagnosis is complicated, and the prognosis is poor.
PNS is significantly associated with high levels of disease activity.
Because it can be disabling, nerve involvement can have a negative impact on the quality of life of patients, and immunosuppressive therapy is often required.
PNS is most affected, especially small fiber neuropathy (SFN) and dorsal root ganglion disease, which are often described as special features; studies have shown that SFN patients are predominantly male, with anti-SSA/RO52/60 antibodies and rheumatoid factor (RF) The frequency of positivity is reduced; anti-SSA/RO-negative patients have a higher prevalence of PNS than positive patients.
6 Joint involvement Joint involvement is one of the most common manifestations of disease.
Among 20% to 60% of pSS patients, about 1/3 develop synovitis similar to rheumatoid arthritis (RA).
Compared with non-synovitis patients, patients with synovitis are characterized by swelling of the parotid glands and a higher frequency of swollen lymph nodes.
pSS-associated arthritis is usually non-invasive, and patients with anti-cyclic citrullinated peptide (CCP) antibodies are at higher risk of RA.
A study showed that anti-CCP antibodies were significantly related to the risk of arthritis and RA development in patients with pSS.
All pSS patients with anti-CCP antibodies did not observe the progress of structural erosion during follow-up; immunosuppressants include hydroxychloroquine and methotrexate Rituxan and rituximab show similarly good effects in reducing pain and joint inflammation.
7 Other autoimmune diseases Compared with the general population, patients with pSS are more likely to suffer from other autoimmune diseases, such as autoimmune thyroiditis and celiac disease.
Primary SS with Hashimoto's thyroiditis (HT) is characterized by a higher incidence of lymphatic structure lesions and urticaria, and anti-RO/SSA antibodies are more common in the pSS group.
Research suggests that young patients with pSS can be considered for CD screening when the disease is diagnosed.
8 Lymphoma The risk of B-cell lymphoma in patients with pSS is 15-20 times that of the general population, which is attributed to chronic B-cell activation in patients with pSS.
These lymphomas are multiple B-cell non-Hodgkin's lymphomas, which often occur in organs where pSS is active, such as the salivary glands.
It is recommended to perform the simplest tests every 1-2 years, such as lymphocyte count, protein electrophoresis, RF, C3 and C4 proteins, and cryoglobulin.
For higher-risk patients, it is recommended to evaluate every 6 months.
When lymphoma is suspected, imaging tests such as PET-CT may be helpful, and the diagnosis requires tissue biopsy.
03 Treatment 1 Fatigue symptoms There is currently no drug proven to be effective for the fatigue of pSS patients.
Non-pharmacological strategies may have potential benefits.
For example, supervised exercise and non-invasive vagus nerve stimulation have been shown to improve fatigue, cardiorespiratory health, and exercise tolerance.
2 The new formula of cyclosporine A (CyA) and sirolimus for the treatment of dry eyes may be superior in bioavailability and effectiveness.
The results of the study show that CyA cationic emulsion has a significant improvement effect on pSS patients with severe dry eye, but has no significant effect on the entire pSS population.
Compared with CyA, sirolimus is more effective, but has poor water solubility, which limits its ability to penetrate the tear film barrier.
3pSS-related lymphoma is currently undergoing multiple clinical trials to test the efficacy of different drugs targeting B cells and T cells.
Indolence: wait and see, cytotoxic therapy, low-dose radiotherapy, surgery, chemotherapy or chemotherapy; aggressiveness: RCHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone).
Biological agents can be used to treat borderline cases that are difficult to clearly diagnose as B-cell malignancies and the pre-lymphoma state of pSS.
A French study showed that about two-thirds of patients treated with rituximab showed systemic improvement, especially those with vasculitis or persistent/recurrent parotid swelling caused by cryoglobulinemia.
Abatacept, Ialiumab, and Ofatumumab may be effective for more severe clinical manifestations.
Finally, there are some new drugs for the excessive proliferation of B cells, including small molecule inhibitors, anti-IL-7 treatments, etc.
, which are in clinical trials and are worth looking forward to.
