Introduction

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterised by inflammation in multiple systems of the body. The prevalence of SLE is higher in people assigned female at birth, with a ratio of 9:1 compared to people assigned male at birth. It typically occurs between the ages of 15 and 45.¹ The precise mechanism of the disease is not fully understood and it differs between individuals. However, it is thought to be caused by the interaction of environmental and genetic factors, triggering an autoimmune response. Monocytosis refers to the abnormally high number of monocytes, a type of white blood cell involved in fighting infections as part of the immune system. Ongoing research shows that monocyte abnormalities are associated with the progression of SLE. 

Overview of SLE

Systemic lupus erythematosus (SLE) is a type of lupus caused by the complex interaction of environmental and genetic factors. Although the exact cause has not been identified, several risk factors may include smoking, infection, stress, hormonal changes and family history. The prevalence of SLE differs globally, with the greatest incidence in North America, and the lowest in Africa. ¹ However this may represent underdiagnosis or misdiagnosis in Africa. 

There are two types of lymphocytes (white blood cells); B cells and T cells. In SLE, the autoimmune response leads to the creation of autoantibodies, antibodies that react with self-antigens, receptors on cells that identify the cell as belonging to that individual, by B Cells. The disease also affects the production of cytokines, another type of protein involved in regulating the immune system. These antibodies mislabel organs and other bodily structures as foreign invaders, causing them to attack these organs, leading to chronic inflammation. The T cells play a large role in the inflammatory aspect of the disease, through the release of pro-inflammatory cytokines. Regulatory Treg cells are one type of T cell that suppress the immune response and are activated by a protein called  interleukin-2 (IL2). SLE leads to decreases in IL2 activity, meaning there are fewer Treg cells present. This causes SLE to progress and worsen. 

A major consequence of SLE is the dysregulation of apoptosis (cell destruction). The increased apoptosis and debris clearance of cells means that there is more antigen exposure, leading to further destruction. Typically, many pathways evolve to prevent this immune action in response to the debris formed, however, this ability is impaired in SLE. As a result, the increased survival of these defected lymphocytes allows the disease to progress and worsen.¹ This can lead to a wide range of symptoms, including fatigue, rashes and joint pain.³

Monocytes in SLE

Monocytes have a significant role in the immune system. These include presenting antigens (foreign substances in the body), to T cells (a type of white blood cell), phagocytosis (the engulfing of material in the cell, helping to kill pathogens), and cytokine production. ²

Monocytes are part of the phagocyte system in innate immunity. They are leukocytes that are produced in the bone marrow and circulate in the blood and spleen. They recognise patterns on receptors, detecting when they are harmful and threatening. Monocytes can destroy antigen-presenting cells, release chemokines and further proliferate as a response to infection and injury.⁴  Monocytosis means that there are a high number of monocytes present in the blood system. This is common in autoimmune diseases. 

However, monocytes CD14+ and CD16+ are not significantly higher in SLE, as they are in Rheumatoid Arthritis.  in which the sufferers had a significantly higher CD14+ and CD16+ count. This may be because these are active at sites of inflammation like the kidneys, so aren’t detected as free-flowing monocytes. They may also be reduced because some treatments for SLE include steroids, which can reduce the monocyte cell count, or because they don’t develop properly in SLE.²

Monocyte abnormalities in SLE

There have been a number of reported abnormalities which lead to dysregulation and contribute to the development and progression of SLE. One such abnormality is the dysregulation of Fc gamma receptors. These are involved in numerous immune mechanisms, including phagocytosis (the engulfing of viruses and bacteria in cells), cytolysis, when the cell bursts and breaks down, degranulation, when antimicrobial molecules are released from the cell, and the release of inflammatory cytokines. The different forms of Fc Gamma receptors are the risk alleles for SLE. A low copy number usually leads to the development of SLE, and a higher one prevents the development. 

Another abnormal finding in patients with SLE, the activating receptor CD64 is overexpressed in their monocyte count, leading to chronic inflammation. To further this, SLE patients’ monocytes display a higher level of ICAM-1, a glycoprotein on the surface of cells responsible for inflammatory cytokine production. This higher level increases inflammation. Individuals with SLE may also have greater levels of CD40. This is a receptor on B cells, which binds to its ligand on T cells. In SLE this can lead to the production of autoantibodies. The final abnormality that monocytes seem to have from SLE, is in their antigen presentation. This misrepresentation causes the decreased expression of certain macrophages. Therefore, understanding the nature of monocytes in SLE can help to explain some of the symptoms of SLE.²

Symptoms and diagnosis of SLE

It is quite difficult to diagnose SLE and it can mean that sometimes the disease can develop in severity before it is identified. This may be due to misdiagnosis, as SLE can present similarly to other diseases, such as rheumatoid arthritis. SLE is characterised by a malar rash, which often forms the shape of a butterfly on the face, however, if the rash isn’t present it can be a lot more difficult to successfully diagnose. Other symptoms may include photosensitive skin rash, patches of rough, scaly skin, oral or nasal ulcers, arthritic joint swelling, fever and seizures.⁵ 

The criteria for a diagnosis of SLE include testing such as:

• Antinuclear antibody testing through immunofluorescence⁵ 
• Key biomarkers: proteinuria, urinary casts, hemolytic anaemia 
• Blood tests: certain monocytes, phagocytes⁶ 

Overall it is quite difficult to accurately diagnose SLE sufferers as it differs from person to person, with certain monocytes and cells being affected. 

Treatment of SLE

One of the main forms of treatment is the medication HydroxyChloroQuine (HCQ). HCQ lowers the risk of disease flare-ups, reducing musculoskeletal complications and skin-related symptoms. HCQ also decreases the risk of thrombosis and improves life expectancy. The side effects include gastrointestinal issues such as diarrhoea, abdominal pain and vomiting. Glucocorticoids, which are steroids, such as prednisone, may also be used periodically to control disease activity, but are used in low doses as they can cause severe damage over long periods of time.⁷ SLE patients may also suffer from rheumatoid arthritis, which is typically treated with an immunosuppressant called methotrexate, which also helps to reduce symptoms of SLE. 

Biological treatments, Belimumab and Rituximab, can also be administered via IV infusion. Belimumab seems to target the B lymphocyte receptor directly, blocking its receptor on B cells, thereby decreasing B cell activation and differentiation. This is different to HCQ, which alters signalling pathways to reduce the release of cytokines and limit inflammation. The newer forms of therapies aim to directly deal with the immune cells. However, it is important to note that all these treatments are immunosuppressant, which makes SLE patients at high risk when it comes to contracting other diseases.⁸

Summary 

To conclude, monocytosis in SLE is not fully understood. However, most of the research suggests that it may have a large influence on the development and progression of the disease. The latest research puts more emphasis on the role of monocytes and their activation of lymphocytes, rather than the case of monocytosis itself. SLE is a very complex disease that is constantly being researched to further understand its mechanism and future treatments of the disease.