The endothelial cells produce cytokines and antimicrobial peptides against the bacteria. These products regulate the coagulation cascade and movements of white blood cells. Macrophages presented in humans are able to engulf Leptospira. However, Leptospira are able to reside and proliferate in the cytoplasmic matrix after being ingested by macrophages. Those with severe leptospirosis can experience a high level of cytokines such as interleukin 6, tumor necrosis factor alpha (TNF-α), and interleukin 10. The high level of cytokines causes sepsis-like symptoms which is life-threatening instead of helping to fight against the infection. Those who have a high risk of sepsis during a leptospirosis infection are found to have the HLA-DQ6 genotype, possibly due to superantigen activation, which damages bodily organs.Leptospira LPS only activates toll-like receptor 2 (TLR2) in monocytes in humans. The lipid A molecule of the bacteria is not recognised by human TLR4 receptors. Therefore, the lack of Leptospira recognition by TLR4 receptors probably contributes to the leptospirosis disease process in humans.Although there are various mechanisms in the human body to fight against the bacteria, Leptospira is well adapted to such an inflammatory condition created by it. In the bloodstream, it can activate host plasminogen to become plasmin that breaks down extracellular matrix, degrades fibrin clots and complemental proteins (C3b and C5) to avoid opsonisation. It can also recruit complement regulators such as Factor H, C4b-binding protein, factor H-like binding protein, and vitronectin to prevent the activation of membrane attack complex on its surface. It also secretes proteases to degrade complement proteins such as C3.
Cardiospondylocarpofacial syndrome is a very rare genetic disorder which is characterized by cardiac, digital, osseous anomalies with facial dysmorphisms

Signs and symptoms
The following is a list of the symptoms most commonly exhibited:
Variable vertebral anomalies
Brachydactyly
Conductive hearing loss
High palate
Mitral regurgitation
Mitral valve prolapse
Short stature, nearing dwarfism
Short palms
Carpal bone synostosisLess common symptoms include:

Failure for permanent teeth to erupt
Teeth misalignment
Horseshoe kidney
Dentition anomalies
Ocular anomalies
Nostril anteversion
Epiphysis in the shape of a cone
Congenital hearing loss
Decresed testes size (males)
Skeletal maturation delay
Feeding difficulties
Freckles
Apple cheeks
Gastroesophageal reflux
Hypertelorism
Joint hypermobility
Long philtrum
Rotated ears
Pseudoepiphyses
High frequency of middle ear infections
Rib synostosis
Scoliosis
Small foot
Strabismus
Tarsal synostosis
Telecanthus
Upslanted parpebral fissures
Broad nasal bridge
Vesicoureteral reflux

Causes
It is caused by autosomal dominant mutations of the MAP3K7 gene in the long arm of chromosome 6. Epidemiology
Only 12 cases worldwide have been described in medical literature. == References ==