Imagine diving into the cool waters of the Seine on a hot summer day, with the Eiffel Toweras a backdrop. This scene, which may seem idyllic, has actually been banned for nearly a century. Yet, as the Paris 2024 Olympic Games approach, the issue of swimming in the Seine is resurfacing, raising both hope and concern.

I. Major health risks 

Swimming in the Seine today is not without danger. Water pollution, mainly of microbiological origin due to viruses, bacteria and parasites, poses significant health risks. Here is an overview of the main dangers to which swimmers are exposed.

A. Gastrointestinal infections 

The water of the Seine is often contaminated by bacteria such as Escherichia coli and enterococci, which are indicators of fecal pollution. These bacteria come mainly from untreated wastewater discharges and animal droppings. Accidental ingestion of this water can lead to gastrointestinal infections, manifested by symptoms such as:

 

• Diarrhea
• Stomach ache
• Nausea
• Vomiting

 

These infections can be particularly serious in vulnerable people, such as children, the elderly and those with weakened immune systems.

B. Skin and ENT infections

Skin contact with polluted water from the Seine can cause various skin and ENT (ear, nose, throat) infections. The risks are increased for people with wounds or skin lesions. Possible infections include:

• Dermatitis: inflammation of the skin that can cause redness, itching and rashes.

• Eye infections: conjunctivitis and other eye inflammations.

• Ear infections: external otitis, often painful and bothersome.

• Throat infections: pharyngitis and other inflammations of the upper respiratory tract.

These infections may require medical treatment and, in some cases, lead to more serious complications.

C. Leptospirosis

Leptospirosis, also known as “rat disease,” is a serious bacterial infection transmitted through contaminated rodent urine. This disease can be contracted through skin or mucous membrane contact with contaminated fresh water. Symptoms of leptospirosis may include:

• High fever
• Severe headaches
• Muscle pain
• Chills
• Vomiting

In the most severe cases, leptospirosis can lead to liver, kidney or meningeal complications, and can be potentially fatal if not treated promptly.

II Current status of water quality

The quality of the Seine's water is a major concern for both authorities and citizens. Despite efforts made in recent years, the current state of the river's water remains problematic, particularly with regard to swimming. Let's take a closer look at the results of recent studies and their significance.

A. Results of recent studies

The NGO Surfrider Foundation, known for its commitment to protecting oceans and waterways, has conducted a series of tests on the water quality of the Seine. The results are revealing of the current state of the river:

• Of the 14 tests carried out, only one was deemed satisfactory according to bathing standards.

• The majority of the samples taken showed levels of bacteriological pollution above the authorised thresholds.

• Concentrations of bacteria such as Escherichia coli frequently exceeded acceptable limits for bathing water.

• These results highlight the persistence of water quality problems, despite the sanitation efforts undertaken.

B. Comparison with legislative standards

European and French legislation sets strict standards for the quality of bathing water. These standards are based on the presence of certain bacteriological indicators, including E. coli and intestinal enterococci. Here is how the Seine ranks according to these standards:

	Sample from June 10, 2024	“Excellent” water quality:	“Sufficient” water quality:
E. COLI:	2216 CFU/100 ML	≤ 500 CFU/100 ML	≤ 900 CFU/100 ML
Intestinal enterococci	563 CFU/100 ML	≤ 200 CFU/100 ML	≤ 330 CFU/100 ML

Tests carried out on the Seine show that these thresholds are regularly exceeded, sometimes significantly. For example, concentrations of CFU/100 ml of E. coli were recorded at the Pont Alexandre III in June 2024, well above the thresholds recommended by the and triathlon federations.

C. Factors influencing water quality

• Wastewater discharges: Despite advances in wastewater treatment, overflows can still occur during heavy rains.
• Urban runoff: Rainwater running off impermeable surfaces in the city carries various pollutants into the river.
• Industrial activity: Although regulated, industry continues to contribute to the pollution of the river.
• River traffic: Boats traveling on the Seine can be a source of pollution, particularly through their discharges.

Conclusion

Swimming in the Seine carries significant health risks due to microbiological and chemical pollution of the water. Gastrointestinal, skin, ENT infections and leptospirosis are the main dangers to which swimmers are exposed. Despite considerable efforts to improve water quality, particularly in view of the Paris 2024 Olympic Games, swimming in the Seine remains prohibited and strongly discouraged without specific authorization.

 The identification of a variant of the TLR7 gene as a cause of lupus erythematosus opens the door to the search for more effective treatments for the disease.

Lupus is an autoimmune disease caused by the activation of the immune system against the body's own tissues, leading to inflammation and damage to joints and certain organs. Its causes include both environmental and genetic factors, which have not yet been characterized in detail.

Currently, lupus is an incurable disease. Although there are treatments aimed at alleviating its symptoms, some of them, which focus on reducing the action of the immune system, have the side effect of increasing patients' susceptibility to infections.

This is one of the main reasons why it is necessary to complete the puzzle of genetic factors that influence its development to a greater or lesser extent. Deciphering the genetic causes of the disease will allow us to better understand the biological mechanisms involved in it and identify points where therapeutic action could be taken.

A recent study led by researchers at the Australian National University, with Spanish direction and participation, has just taken a very important step towards better understanding lupus.

The researchers have identified a genetic cause of the disease that offers a new path for the development of treatments: the presence of gain-of-function variants in TLR7, a gene involved in protecting the immune system against viral infections. The results are published in Nature.

Identifying the connection between TLR7 and lupus

The TLR7 gene encodes a receptor, also called TLR7, that recognizes single-stranded RNA molecules derived from viruses and bacteria and activates the immune system in response. In addition, it can also be activated by the nucleoside guanosine and its endogenous derivatives, although this does not normally represent a threat to health because it occurs to a lesser extent.

Previous studies had already suggested that TLR7 function played a role in systemic lupus. Increased activity had been found in some B lymphocytes from patients and some common polymorphisms were associated with the disease. However, until now no genetic change had been identified in the TLR7 gene that had a determining effect on the onset of lupus.

The first direct link between the TLR7 gene and lupus was found when sequencing the genome of Gabriela, a young Spanish girl who had been diagnosed with a severe case of the disease at the age of 7. The severity and early onset of lupus led researchers to believe that it must be a case caused by a single genetic mutation.

By analysing Gabriela's entire genome, the researchers found a variant in the TLR7 gene that was likely to cause lupus: p.Tyr264His. Various elements pointed to the variant as being responsible for the young woman's disease: the variant caused an amino acid change, it was located in a region of the protein conserved between species, and the computer programs used to predict its effects indicated that it was a harmful variant.

As further evidence, the researchers found two more variants in TLR7 when analyzing the whole exome of other patients with systemic lupus, without detecting changes in any other known lupus-related genes in the implicated families.

Mutation causes lupus when introduced into mice

Based on functional studies in cells, the researchers found that the presence of the p.Tyr264His variant produces a TLR7 protein with greater affinity towards certain endogenous ligands with guanosine that, normally, would not activate the protein, which could explain the development of the autoimmune reaction characteristic of lupus.

To confirm the mutation's role in the development of lupus, the researchers introduced the mutation into mice, creating a strain they named kika, in reference to the name Gabriela had given to a stuffed animal she had been given during one of her hospital visits.

The team observed that the mutation (also called kika) was enough to cause lupus in the animals, which developed different autoimmune symptoms and experienced various organ damage.

The results explain why lupus is more common in women

The study also offers an explanation for why 9 out of 10 people with lupus are women. The TLR7 gene is located on the X chromosome, so that people with a male chromosomal sex have one copy, while those with a female sex have two.

As a biological mechanism of dosage compensation, in women one of the two X chromosomes is inactivated in their cells. However, TLR7 escapes inactivation in immune cells, which leads to the fact that in women there may be two active copies compared to the single copy present in male cells.

Thus, if there is an autoimmune response influenced by TLR7, the effect may be greater in women. And if, in addition, they are carriers of a variant that increases the affinity towards endogenous ligands such as the p.Tyr264His variant, its impact would be even greater.

The opposite example has been observed in the case of the response to SARS-CoV-2 infection, where the presence of genetic variants that produce a deficiency in TLR7 has been linked to a higher risk of developing COVID-19 in men.

Relevance for the development of therapies for lupus and other autoimmune diseases

The study shows that the identified TLR7 gain-of-function variant is sufficient to induce lupus, at least in mice. This result, together with previous data, offers an important step forward for the development of therapies for the disease.

“Even though there are only a small number of people with lupus who have variants in the TLR7 gene, we know that many patients have signs of overactivity in the TLR7 pathway,” said Nan Shen, co-director of the China-Australia Centre for Personalised Immunology, who was involved in the study. “By confirming a causal connection between the gene mutation and the disease, we can begin to look for more effective treatments.”

The team is currently working with pharmaceutical companies to develop or adapt treatments targeting the TLR7 gene that could be beneficial for lupus patients.

These treatments could also be relevant for other autoimmune diseases. “There are other systemic autoimmune diseases such as rheumatoid arthritis and dermatomyositis that fit into the same family as lupus,” says Carola Vinuesa, a researcher at the Australian Centre for Personalised Immunology, co-director of the China-Australia Centre for Personalised Immunology and director of the work.

“TLR7 could also play a role in these conditions,” says the researcher, who has formed a new research team at the Francis Crick Institute focused on identifying the mechanisms that contribute to the development of autoimmunity.

Another question that researchers point out as pending resolution is whether certain environmental stimuli such as the presence of viruses that can activate TLR7 (as is the case with SARS-CoV-2, responsible for COVID-19) can exacerbate the effect of the variant.

Reference: Brown, GJ, Cañete, PF, Wang, H. et al. TLR7 gain-of-function genetic variation causes human lupus. Nature. 2022. DOI: https://doi.org/10.1038/s41586-022-04642-z

 Immune thrombocytopenia (ITP) is a disease caused by the destruction of platelets or thrombocytes by the immune system itself. It is therefore an autoimmune disease.

There are different levels of severity and symptoms of ITP depending on the platelet count. The disease is characterised by an increased risk of bleeding. Platelet levels of between 150,000 and 400,000 per microlitre are considered normal.

When these levels decrease temporarily or persistently, without known triggering factors, then we speak of primary ITP. If the platelet count is below these levels, but above 50,000, it is normally asymptomatic and does not cause bleeding. In these cases, the disease will be difficult to diagnose.

If the platelet count is between 30,000 - 50,000, small hemorrhages often occur when there is trauma, blow, etc. If the count is between 10,000 - 30,000, petechiae, metrorrhagia, epistaxis, gingivorrhagia, etc. may occur spontaneously.

In this situation we speak of moderate thrombocytopenia. If the levels fall below 10,000 platelets per microliter, we are dealing with severe thrombocytopenia in which internal bleeding can occur in vital organs with serious consequences.

The origin of primary immune thrombocytopenia is unknown; although there are other forms of secondary thrombocytopenia associated with certain diseases, infections or the taking of certain medications.

Why does immune thrombocytopenia occur?

The decrease in platelet levels is due both to an increased destruction of platelets in the blood and to a defect in their production in the bone marrow. People who suffer from this disease possess certain antibodies, usually of the IgG type (although in some cases IgM and IgA are also involved), which are capable of recognizing certain proteins on the surface of these cells and marking them as if they were foreign elements to the body itself (antigens).

Consequently, platelets and their precursors in the bone marrow are recognized and eliminated by cells of the immune system, such as macrophages.

What precautions should a person with TPI take?

Physical activity should be controlled and free of dangers such as risky or contact sports, which can cause trauma. It is advisable to ask the doctor which activities should be avoided according to the person's lifestyle.

There are medications that can alter platelet activity, which is why it is always a good idea to ask your doctor before taking any medication.

Keeping the immune system in good condition is important to ensure that its response is balanced and that hypo and hyperactivity situations do not occur. In this regard, microimmunotherapy can be a support within a global strategy for treating immune diseases.

Bibliography

1. Karam D. Echevarría S. Diagnosis and treatment of immune thrombocytopenic purpura. Clinical practice guide. Mexican Social Security Institute.
2. Mayo Clinic. Idiopathic thrombocytopenic purpura. Patient Care and Health Information. Diseases & Conditions. Available at: https://www.mayoclinic.org/diseases-conditions/idiopathic-thrombocytopenic-purpura/symptoms-causes/syc-20352325.

  Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation of the joints. It is sometimes confused with osteoarthritis, but they are different inflammatory diseases.

It affects women to a greater extent, possibly due to the influence of estrogens in the generation of inflammation. In addition, women are more susceptible to autoimmune diseases due to methylation of the X chromosome. There is also a certain heredity with regard to connective tissue diseases, so having a mother with a history of the disease is a risk factor.

Rheumatoid arthritis causes pain, stiffness, swelling, and can even cause joint deformity and loss of normal joint movement. It can also be accompanied by fatigue, occasional episodes of fever, or other symptoms such as heart complications, osteoporosis, or lung complications.

The exact causes of this disease are still not fully understood, although it has been shown that the immune system plays a key role in its development and progression. A combination of genetic and environmental factors triggers an abnormal immune response that results in the production of autoantibodies and chronic activation of the immune system. Let's see what happens to the immune system.

The Adaptive Immune Response in Arthritis

The adaptive response  plays a crucial role in this joint disease. Both B cells and T cells, specialized lymphocytes, are altered and are key in the development of the pathology.

Specifically, an increase in CD4+ T cells and a decrease in Regulatory T cells, responsible for maintaining tolerance and preventing immune reactivity to structures and tissues, have been observed in the affected joints. CD4+ T cells produce proinflammatory cytokines such as interleukin 6, tumor necrosis factor alpha (TNF-α), and interferon gamma. All contribute to chronic inflammation and joint destruction.

B cells also play an important role. Immune complexes consisting of autoantibodies and antigens have been found in the joints of people with this disease. Especially B cells producing anti-citrullinated peptide antibodies (ACPA), are closely associated with disease severity and joint destruction in RA.

In addition, B cells can activate T cells and give rise to a vicious circle that perpetuates the inflammatory response.

Proinflammatory environment and cytokines in arthritis

Chronic inflammation is a hallmark symptom of rheumatoid arthritis. The synovial inflammation typical of arthritis has been shown to be mediated by excessive production of proinflammatory cytokines. These cytokines include IL-1β, IL-6, TNF-α, and IL-17, among others.

They promote the migration of inflammatory cells to the joints and stimulate the production of enzymes that degrade cartilage and bone. TNF-α is one of the most studied cytokines in this disease and has been identified as an important therapeutic target to reduce inflammation and disease progression in these patients.

Solving the Immunological Puzzle

Rheumatoid arthritis is a complex autoimmune disease that involves a dysfunctional adaptive immune response and chronic inflammation of the joints. It must be treated by specialists to prevent it from progressing to other locations and to maintain joint functionality.

Many of the available treatments usually help to relieve symptoms, although they do not always treat the root of the problem. In this regard, it is also worth considering approaches that allow the mediators involved to be modulated simultaneously, trying to redirect the immune response both locally and systemically, so that it works optimally, depending on each person's situation.

Immunomodulatory treatments are an option to consider in this case, since they can offer complementary support to symptomatic relief, helping to rebalance inflammatory signaling.

This is precisely the goal of microimmunotherapy. Doctors who use it in patients with rheumatoid arthritis seek to counteract the deregulation that exists in the inflammatory response and its persistence, in order to limit the deterioration of the affected tissue.

It should be noted that microimmunotherapy is based on the use of the same type of molecules and immunological mediators that the immune system uses, in low and very low doses, to work from a physiological point of view, coming as close as possible to the natural functioning of the body.

For example, it can be aimed at down-regulating the action of cytokines such as IL-1 or IL-6, involved in the inflammatory reaction.

In the end, in rheumatoid arthritis as in other autoimmune diseases, it is not just a matter of slowing down immunity, but of returning it to a state of balance.

Bibliography

1. Miguel-Lavariega D, Elizararrás-Rivas J, Villarreal-Ríos E, Baltiérrez-Hoyos R, Velasco-Tobón U, Vargas-Daza ER, Galicia-Rodríguez L. Epidemiological profile of rheumatoid arthritis. Rev Med Inst Mex Seguro Soc. 2023 Sep 4;61(5):574-582. Spanish. doi: 10.5281/zenodo.8316427.
2. van Delft MAM, Huizinga TWJ. An overview of autoantibodies in rheumatoid arthritis. J Autoimmun. 2020 Jun;110:102392. doi: 10.1016/j.jaut.2019.102392. Epub 2020 Jan 3.
3. Radu AF, Bungau SG. Management of Rheumatoid Arthritis: An Overview. Cells. 2021 Oct 23;10(11):2857. doi:10.3390/cells10112857.