The pannus is an abnormal layer of tissue that can form in the joints of individuals with rheumatoid arthritis (RA). RA causes synovitis — inflammation of the protective tissue that lines joints (called the synovium) — and excess synovial fluid buildup. This excess synovial tissue can form the pannus, which can be damaging to the joint.

The rheumatology field has long attempted to understand what the pannus is and what it does. Pannus was originally seen with magnetic image resonance in 1994, but how it works has been studied for decades.

Today, it’s understood that the pannus is not a separate tissue that develops during RA. Instead, it’s a state of the inflamed synovial tissue that in itself contributes to the inflammatory disease of RA. The pannus is made of a complex community of cells, each of which plays a role in driving inflammation and joint damage. A pannus is not permanent and can be reversed through RA treatment. Advancing treatments for RA may target the specific cells involved in the formation of the pannus.

The Anatomy of the Joint

There are several types of joints in the body, but the general organization of every joint is similar. The bones in a joint are covered in articular cartilage, which protects the bones from friction. The synovium or synovial membrane surrounds and seals the joint. The synovium makes a clear fluid called synovial fluid that fills the joint space to lubricate it. In healthy joints, the synovium has two or three layers of cells. Ligaments surround joints to support them and connect bones together. Tendons attach muscles to the bones so that the joint can move.

Many different types of cells live inside the joints and have different jobs to keep joints healthy and functional. Some of these cells include:

• Type A synoviocytes — Also known as macrophage-like synovial cells, these are part of the family of immune-system cells called leukocytes. They are responsible for clearing out waste and debris in the joint, as well as viruses and bacteria.
• Type B synoviocytes — Also known as fibroblast-like synoviocytes (FLS), these cells make the collagens and synovial fluid of the joint.
• Osteoblasts — These cells make new bone.
• Osteoclasts — These are responsible for reabsorbing old bone. They also work with osteoblasts to maintain bone health.
• Chondrocytes — These work to sustain the cartilage in the joint.

All of these cells are responsible for keeping joints healthy. With RA, these cells act differently and can actually change how the joint tissue functions in response to disease and damage.

Formation of the Pannus

Researchers are not sure how or why RA starts, but when the immune system begins attacking the joint, the synovium becomes inflamed. As a result, cells in the joint are altered and contribute to the development of disease. More type A cells enter the joint from the bone marrow.

These inflammatory cells produce several signals to:

• Attract more cells (through chemokines)
• Increase inflammation (through proinflammatory cytokines)
• Increase growth of the joint tissue (through growth factors)

The type A cells contribute to the activation of the type B (FLS) cells to also create inflammation signals. These cells keep recruiting more cells to the joint, which contributes to the destruction of the joint tissue.

The expanded, destructive synovial tissue is called a pannus, which is Latin for “cloth." The pannus tissue is similar to a tumor lesion because it shows rapid and invasive growth.

Several processes contribute to the rapid tissue growth of the pannus. Although normal synovium usually does not have blood vessels, the cells in the pannus drive a process called angiogenesis, which is the growth of new blood vessels into the joint. This process is also common in tumor-like tissues. New blood vessels help more cells move into the pannus tissue. Whereas healthy synovium has two or three layers of cells, the rheumatoid synovium can have 10 to 20 layers of cells. The increase in the number of cells in a tissue is called hyperplasia and is a common feature of cancer-like tissues. Several of the cell types directly contribute to joint destruction.

Cells Involved in Pannus Formation and Joint Destruction

There are several types of cells involved in pannus formation and joint destruction. These include T cells, B cells, osteoclasts, and FLS cells.

T Cells and B Cells

T cells and B cells are part of a family of white blood cells called lymphocytes. These cells work together to attack bacteria and viruses when presented with an antigen (a marker of a harmful substance). T cells and B cells move into the pannus and are activated by some unknown antigen to make autoantibodies, like rheumatoid factor and anti-citrullinated protein antibodies — antibodies that contribute to attacking the joints.

Osteoclasts

Osteoclasts are activated by signals produced by other cells, like tumor necrosis factor. They are mainly responsible for the destruction of bone in RA. In rheumatoid joints, osteoclast cells absorb more bone than they are supposed to, leading to bone loss.

FLS Cells

In RA, FLS cells play a large part in pannus formation and cartilage destruction. FLS cells create several signals that contribute to inflammation and pannus growth, like interleukins. They might also help T cells and B cells make the antibodies that attack the joint. FLS cells may keep the T cells and B cells alive longer by producing inhibitors of cell death (apoptosis), allowing the immune cells to live longer.

FLS cells directly attack cartilage in the joints as well. The FLS cells stick to cartilage, then release enzymes that degrade the cartilage.

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